PubMed

Zhongguo Dang Dai Er Ke Za Zhi. 2024 Jun 15;26(6):575-583. doi: 10.7499/j.issn.1008-8830.2309129.ABSTRACTOBJECTIVES: To study the characteristics and clinical value of intestinal metabolites in children aged 4-6 years with obstructive sleep apnea-hypopnea syndrome (OSAHS).METHODS: A total of 31 children aged 4-6 years with OSAHS were prospectively enrolled as the test group, and 24 healthy children aged 4-6 years were included as the control group. Relevant clinical indicators were recorded. Fecal samples were collected, and non-targeted metabolomics analysis using liquid chromatography-mass spectrometry was performed to detect all metabolites.RESULTS: A total of 206 metabolites were detected, mainly amino acids and their derivatives. There was a significant difference in the overall composition of intestinal metabolites between the test and control groups (P<0.05). Eighteen different metabolites were selected, among which six (N-acetylmethionine, L-methionine, L-lysine, DL-phenylalanine, L-tyrosine, and L-isoleucine) had receiver operating characteristic curve areas greater than 0.7 for diagnosing OSAHS. Among them, N-acetylmethionine had the largest area under the curve, which was 0.807, with a sensitivity of 70.83% and a specificity of 80.65%. Correlation analysis between different metabolites and clinical indicators showed that there were positive correlations between the degree of tonsil enlargement and enterolactone, between uric acid and phenylacetaldehyde, between blood glucose and acetylmethionine, and between cholesterol and 9-bromodiphenyl and procaine (P<0.05). There were negative correlations between the degree of tonsil enlargement and N-methyltyramine, aspartate aminotransferase and indolepropionic acid and L-isoleucine, between alanine aminotransferase and DL-phenylalanine, between indolepropionic acid and L-isoleucine, between uric acid and hydroxyquinoline, and between urea nitrogen and N,N-dicyclohexylurea (P<0.05). The metabolic functional pathways affected by differential metabolites mainly included riboflavin metabolism, arginine and proline metabolism, pantothenic acid and coenzyme A biosynthesis, cysteine and methionine metabolism, lysine degradation and glutathione metabolism.CONCLUSIONS: Intestinal metabolites and metabolic functions are altered in children aged 4-6 years with OSAHS, primarily involving amino acid metabolism disorders. The screened differential intestinal metabolites have potential screening and diagnostic value as biomarkers for OSAHS.PMID:38926373 | DOI:10.7499/j.issn.1008-8830.2309129

Discov Med. 2024 Jun;36(185):1268-1279. doi: 10.24976/Discov.Med.202436185.117.ABSTRACTBACKGROUND: Tuberculosis (TB) stands as the second most prevalent infectious agent-related cause of death worldwide in 2022, trailing only COVID-19. With 1.13 million reported deaths, this figure is more than half of the mortality associated with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), which accounted for 0.63 million deaths. Diagnosing Mycobacterium tuberculosis (MTB) infection remains a formidable challenge due to the inability to isolate and detect MTB in sputum and within the human body. The absence of universally reliable diagnostic criteria for MTB infection globally poses a significant obstacle to preventing the progression of tuberculosis from the MTB infection stage.METHODS: In this study, our objective was to formulate a diagnostic biomarker cluster capable of discerning the progression of MTB infection and disease. This was achieved through a comprehensive joint multiomics analysis, encompassing transcriptome, proteome, and metabolome, conducted on lung tissue samples obtained from both normal control mice and those infected with MTB.RESULTS: A total of 1690 differentially expressed genes and 94 differentially expressed proteins were systematically screened. From this pool, 10 core genes were singled out. Additionally, eight long non-coding ribonucleic acids and eight metabolites linked to these core genes were identified to establish a cohesive cluster of biomarkers. This multiomics-based biomarker cluster demonstrated its capability to differentiate uninfected samples from MTB-infected samples effectively in both principle component analysis and the construction of a random forest model.CONCLUSION: The outcomes of our study strongly suggest that the multiomics-based biomarker cluster holds significant potential for enhancing the diagnosis of MTB infection.PMID:38926113 | DOI:10.24976/Discov.Med.202436185.117

Anim Reprod Sci. 2024 Jun 18:107539. doi: 10.1016/j.anireprosci.2024.107539. Online ahead of print.ABSTRACTThe last decades of research have revealed that many other factors besides gamete genomes are able to determine the reproductive outcomes. Indeed, paternal factors have been observed to be capable of modulating multiple crucial features of the reproductive process, such as sperm physiology, the maternal environment and, even, the offspring health. These recent advances have been encompassed with the emergence of OMICS technologies, as they comprehensively characterise the molecular composition of biological systems. The present narrative review aimed to take a closer look at the potential of these technologies in the field of reproductive biology. This literature revision shows that most studies up to date have followed a non-targeted approach to screen mammalian seminal plasma (SP) and sperm metabolite composition through different metabolome platforms. These studies have proposed metabolites of multiple natures as potential in vivo fertility biomarkers. Yet, targeted approaches can be used to answer specific biological question, and their power is exemplified herein. For instance, metabolomic studies have uncovered not only that glycolysis is the main ATP energy source of pig sperm, but also that sperm metabolism can trigger DNA damage, hence compromise embryo development. In conclusion, this review shows the potential of both non-targeted and targeted metabolomics for the discovery of cell pathways that govern the reproductive process. Understanding these systems could help make progress in different areas, including livestock efficient breeding, the improvement of artificial reproductive technologies, and the development of biomarkers for infertility detection.PMID:38926002 | DOI:10.1016/j.anireprosci.2024.107539

Ann Clin Transl Neurol. 2024 Jun 24. doi: 10.1002/acn3.52131. Online ahead of print.ABSTRACTOBJECTIVE: Transcranial sonography (TCS) is a noninvasive neuroimaging technique, visualizing deep brain structures and the ventricular system. Although widely employed in diagnosing various movement disorders, such as Parkinson's disease and dystonia, by detecting disease-specific abnormalities, the specific characteristics of the TCS in cerebellar ataxia remain inconclusive. We aimed to assess the potential value of TCS in patients with cerebellar ataxias for disease diagnosis and severity assessment.METHODS: TCS on patients with genetic and acquired cerebellar ataxia, including 94 with spinocerebellar ataxias (SCAs) containing 10 asymptomatic carriers, 95 with cerebellar subtype of multiple system atrophy (MSA-C), and 100 healthy controls (HC), was conducted. Assessments included third ventricle width, substantia nigra (SN) and lentiform nucleus (LN) echogenicity, along with comprehensive clinical evaluations and genetic testing.RESULTS: The study revealed significant TCS abnormalities in patients with cerebellar ataxia, such as enlarged third ventricle widths and elevated rates of hyperechogenic SN and LN. TCS showed high accuracy in distinguishing patients with SCA or MSA-C from HC, with an AUC of 0.870 and 0.931, respectively. TCS abnormalities aided in identifying asymptomatic SCA carriers, effectively differentiating them from HC, with an AUC of 0.725. Furthermore, third ventricle width was significantly correlated with SARA and ICARS scores in patients with SCA3 and SCOPA-AUT scores in patients with MSA-C. The SN area and SARA or ICARS scores in patients with SCA3 were also positively correlated.INTERPRETATION: Our findings illustrate remarkable TCS abnormalities in patients with cerebellar ataxia, serving as potential biomarkers for clinical diagnosis and progression assessment.PMID:38924300 | DOI:10.1002/acn3.52131

Biomed Chromatogr. 2024 Jun 26:e5941. doi: 10.1002/bmc.5941. Online ahead of print.ABSTRACTMitomycin C (MMC) has an antitumor effect and is considered as a broad-spectrum antibiotic. Sijunzi Decoction (SJZD), a well-known ancient Chinese prescription, is widely used in the treatment of cancer when combined with chemotherapy drugs. Studies have shown that SJZD can be combined with other drugs to enhance the therapeutic effect against cancer and inhibit the toxicity of chemotherapy drugs, but the specific mechanism is not clear. Thus, we hope to further explore the antitumor mechanism of combined SJZD and MMC. 3-(4,5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, western blot, 1H NMR and HPLC-MS were used to study the mechanism at the cellular level. The results show that the combined administration can have a more significant effect on inhibiting the proliferation of cancer cells, promoting their apoptosis. Based on metabolomics, 38 biomarkers were found in the MMC group and 43 biomarkers were found in the combined administration group. Among them, 18 unique biomarkers were discovered in the combined administration group. Studies have shown that the antitumor mechanism of combined administration is related to amino acid metabolism, energy metabolism, lipid metabolism and nucleotide metabolism, among which amino acid metabolism is the most important. In addition, SJZD achieves the effect of toxin reduction and efficiency enhancement by improving the body's immunity and improving the oxidative stress environment.PMID:38924132 | DOI:10.1002/bmc.5941

Plant Cell Environ. 2024 Jun 26. doi: 10.1111/pce.15016. Online ahead of print.ABSTRACTThe rice Zaxinone Synthase (ZAS) gene encodes a carotenoid cleavage dioxygenase (CCD) that forms the apocarotenoid growth regulator zaxinone in vitro. Here, we generated and characterized constitutive ZAS-overexpressing rice lines, to better understand ZAS role in determining zaxinone content and regulating growth and architecture. ZAS overexpression enhanced endogenous zaxinone level, promoted root growth and increased the number of productive tillers, leading to about 30% higher grain yield per plant. Hormone analysis revealed a decrease in strigolactone (SL) content, which we confirmed by rescuing the high-tillering phenotype through application of a SL analogue. Metabolomics analysis revealed that ZAS overexpressing plants accumulate higher amounts of monosaccharide sugars, in line with transcriptome analysis. Moreover, transgenic plants showed higher carbon (C) assimilation rate and elevated root phosphate, nitrate and sulphate level, enhancing the tolerance towards low phosphate (Pi). Our study confirms ZAS as an important determinant of rice growth and architecture and shows that ZAS regulates hormone homoeostasis and a combination of physiological processes to promote growth and grain yield, which makes this gene an excellent candidate for sustainable crop improvement.PMID:38924092 | DOI:10.1111/pce.15016

Phytochem Anal. 2024 Jun 24. doi: 10.1002/pca.3412. Online ahead of print.ABSTRACTINTRODUCTION: Compound annotation is always a challenging step in metabolomics studies. The molecular networking strategy has been developed recently to organize the relationship between compounds as a network based on their tandem mass (MS2) spectra similarity, which can be used to improve compound annotation in metabolomics analysis.OBJECTIVE: This study used Bupleuri Radix from different geographic areas to evaluate the performance of molecular networking strategy for compound annotation in liquid chromatography-mass spectrometry (LC-MS)-based metabolomics.METHODOLOGY: The Bupleuri Radix extract was analyzed by LC-quadrupole time-of-flight MS under MSe acquisition mode. After raw data preprocessing, the resulting dataset was used for statistical analysis, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The chemical makers related to the sample growth place were selected using variable importance in projection (VIP) > 2, fold change (FC) > 2, and p < 0.05. The molecular networking analysis was applied to conduct the compound annotation.RESULTS: The score plots of PCA showed that the samples were classified into two clusters depending on their growth place. Then, the PLS-DA model was constructed to explore the chemical changes of the samples further. Sixteen compounds were selected as chemical makers and tentatively annotated by the feature-based molecular networking (FBMN) analysis.CONCLUSION: The results showed that the molecular networking method fully exploits the MS information and is a promising tool for facilitating compound annotation in metabolomics studies. However, the software used for feature extraction influenced the results of library searching and molecular network construction, which need to be taken into account in future studies.PMID:38923688 | DOI:10.1002/pca.3412

Cell Rep. 2024 Jun 25;43(7):114410. doi: 10.1016/j.celrep.2024.114410. Online ahead of print.ABSTRACTPolymyxins are often the only effective antibiotics against the "Critical" pathogen Acinetobacter baumannii. Worryingly, highly polymyxin-resistant A. baumannii displaying dependence on polymyxins has emerged in the clinic, leading to diagnosis and treatment failures. Here, we report that arginine metabolism is essential for polymyxin-dependent A. baumannii. Specifically, the arginine degradation pathway was significantly altered in polymyxin-dependent strains compared to wild-type strains, with critical metabolites (e.g., L-arginine and L-glutamate) severely depleted and expression of the astABCDE operon significantly increased. Supplementation of arginine increased bacterial metabolic activity and suppressed polymyxin dependence. Deletion of astA, the first gene in the arginine degradation pathway, decreased phosphatidylglycerol and increased phosphatidylethanolamine levels in the outer membrane, thereby reducing the interaction with polymyxins. This study elucidates the molecular mechanism by which arginine metabolism impacts polymyxin dependence in A. baumannii, underscoring its critical role in improving diagnosis and treatment of life-threatening infections caused by "undetectable" polymyxin-dependent A. baumannii.PMID:38923457 | DOI:10.1016/j.celrep.2024.114410

Animal Model Exp Med. 2024 Jun 25. doi: 10.1002/ame2.12462. Online ahead of print.ABSTRACTBACKGROUND: To explore potential biomarkers for early diagnosis of atherosclerosis (AS) and provide basic data for further research on AS, the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically.METHODS: An AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet. Fasting serum samples were collected monthly for metabolomics and serum lipid detection. At the end of the treatment period, pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS, thereby distinguishing the susceptibility of mini-pigs to AS. The metabolomics was detected using a high-resolution untargeted metabolomic approach. Statistical analysis was used to identify metabolites associated with AS susceptibility.RESULTS: Based on pathological analysis, mini-pigs were divided into two groups: a susceptible group (n = 3) and a non-susceptible group (n = 6). A total of 1318 metabolites were identified, with significant shifting of metabolic profiles over time in both groups. Dynamic monitoring analysis highlighted 57 metabolites that exhibited an obvious trend of differential changes between two groups with the advance of time. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis indicated significant disorders in cholesterol metabolism, primary bile acid metabolism, histidine metabolism, as well as taurine and hypotaurine metabolism.CONCLUSIONS: During the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet, the alterations in serum metabolic profile exhibited a time-dependent pattern, accompanied by notable disturbances in lipid metabolism, cholesterol metabolism, and amino acid metabolism. These metabolites may become potential biomarkers for early diagnosis of AS.PMID:38923366 | DOI:10.1002/ame2.12462

Plant Biotechnol J. 2024 Jun 24. doi: 10.1111/pbi.14412. Online ahead of print.ABSTRACTOil-Camellia (Camellia oleifera), belonging to the Theaceae family Camellia, is an important woody edible oil tree species. The Camellia oil in its mature seed kernels, mainly consists of more than 90% unsaturated fatty acids, tea polyphenols, flavonoids, squalene and other active substances, which is one of the best quality edible vegetable oils in the world. However, genetic research and molecular breeding on oil-Camellia are challenging due to its complex genetic background. Here, we successfully report a chromosome-scale genome assembly for a hexaploid oil-Camellia cultivar Changlin40. This assembly contains 8.80 Gb genomic sequences with scaffold N50 of 180.0 Mb and 45 pseudochromosomes comprising 15 homologous groups with three members each, which contain 135 868 genes with an average length of 3936 bp. Referring to the diploid genome, intragenomic and intergenomic comparisons of synteny indicate homologous chromosomal similarity and changes. Moreover, comparative and evolutionary analyses reveal three rounds of whole-genome duplication (WGD) events, as well as the possible diversification of hexaploid Changlin40 with diploid occurred approximately 9.06 million years ago (MYA). Furthermore, through the combination of genomics, transcriptomics and metabolomics approaches, a complex regulatory network was constructed and allows to identify potential key structural genes (SAD, FAD2 and FAD3) and transcription factors (AP2 and C2H2) that regulate the metabolism of Camellia oil, especially for unsaturated fatty acids biosynthesis. Overall, the genomic resource generated from this study has great potential to accelerate the research for the molecular biology and genetic improvement of hexaploid oil-Camellia, as well as to understand polyploid genome evolution.PMID:38923257 | DOI:10.1111/pbi.14412

Int J Rheum Dis. 2024 Jun;27(6):e15218. doi: 10.1111/1756-185X.15218.ABSTRACTOBJECTIVE: Alterations in gut microbiota have been implicated in the pathogenesis of ankylosing spondylitis (AS), but the underlying mechanisms remain elusive. This study aims to investigate changes in gut microbiota and metabolites in individuals with AS before and after treatment with secukinumab, to identify the biological characteristics specific to AS patients and investigate the potential biomarkers, for optimizing therapeutic strategies more effectively.METHODS: Fecal microbiome data were collected from 30 AS patients before and after secukinumab therapy and compared with data from 40 healthy controls (HC). Additionally, we analyzed the metabolic profile of both groups from plasma.RESULTS: Findings indicated that the treatment-induced changes in the composition of several crucial bacterial groups, including Megamonas, Prevotella_9, Faecalibacterium, Roseburia, Bacteroides, and Agathobacter. Post-treatment, these groups exhibited a distribution more akin to that of the healthy populations compared with their pretreatment status. We identified three gut microbial taxa, namely Prevotellaceae_bacterium_Marseille_P2831, Prevotella_buccae, and Elusimicrobiota, as potential biomarkers for diagnosing individuals at a higher risk of developing AS and assessing disease outcomes. Plasma metabolomics analysis revealed 479 distinct metabolites and highlighted three disrupted metabolic pathways. Integration of microbiome and metabolomics datasets demonstrated a significant degree of correlation, underscoring the impact of the microbiome on metabolic activity.CONCLUSION: Secukinumab can restore the balance of the gut microbiome and metabolites in AS patients, rendering them more similar to those found in the healthy population. The analysis of microbiome and metabolomics data have unveiled some candidate biomarkers capable of evaluating treatment efficacy.PMID:38923187 | DOI:10.1111/1756-185X.15218

Plant J. 2024 Jun 23. doi: 10.1111/tpj.16885. Online ahead of print.ABSTRACTAnalysis of salinity tolerance processes in wheat has focused on salt exclusion from shoots while root phenotypes have received limited attention. Here, we consider the varying phenotypic response of four bread wheat varieties that differ in their type and degree of salt tolerance and assess their molecular responses to salinity and changes in root cell wall lignification. These varieties were Westonia introgressed with Nax1 and Nax2 root sodium transporters (HKT1;4-A and HKT1;5-A) that reduce Na+ accumulation in leaves, as well as the 'tissue tolerant' Portuguese landrace Mocho de Espiga Branca that has a mutation in the homologous gene HKT1;5-D and has high Na+ concentration in leaves. These three varieties were compared with the relatively more salt-sensitive cultivar Gladius. Through the use of root histochemical analysis, ion concentrations, as well as differential proteomics and targeted metabolomics, we provide an integrated view of the wheat root response to salinity. We show different metabolic re-arrangements in energy conversion, primary metabolic machinery and phenylpropanoid pathway leading to monolignol production in a genotype and genotype by treatment-dependent manner that alters the extent and localisation of root lignification which correlated with an improved capacity of wheat roots to cope better under salinity stress.PMID:38923138 | DOI:10.1111/tpj.16885

Plant Cell Environ. 2024 Jun 23. doi: 10.1111/pce.14996. Online ahead of print.ABSTRACTEmerald ash borer (EAB, Agrilus planipennis) is an invasive killer of ash trees (Fraxinus spp.) in North America and Europe. Ash species co-evolved with EAB in their native range in Asia are mostly resistant, although the precise mechanism(s) remain unclear. Very little is also known about EAB or ash tree microbiomes. We performed the first joint comparison of phloem mycobiome and metabolites between a native and a nonnative ash species, infested and uninfested with EAB, in conjunction with investigation of larval mycobiome. Phloem mycobiome communities differed between the tree species, but both were unaffected by EAB infestation. Several indicator taxa in the larval gut shared a similarly high relative abundance only with the native host trees. Widely targeted metabolomics revealed 24 distinct metabolites in native trees and 53 metabolites in nonnative trees, respectively, that differed in relative content between infested and uninfested trees only in one species. Interestingly, four metabolites shared a strong relationship with the phloem mycobiomes, majority of which affected only the native trees. Collectively, our results demonstrate a complex interplay between host tree chemistry and mycobiome, and suggest the shared relationships between the mycobiomes of the native host tree and EAB may reflect their shared co-evolution.PMID:38922989 | DOI:10.1111/pce.14996

J Food Sci. 2024 Jun 26. doi: 10.1111/1750-3841.17147. Online ahead of print.ABSTRACTMung bean sprouts are widely consumed as a seasonal fresh vegetable, renowned for their affordability and richness in antioxidants and bioactive compounds. This study employed ultra-high-performance liquid chromatogram-Q-Exactive HF mass spectrometry (UHPLC-QE-MS) and multivariate statistical analysis to comprehensively evaluate the chemical profile of mung bean sprouts following sulfite immersion. The findings revealed a significant alteration in the overall chemical composition of mung bean sprouts following sodium sulfite immersion. Eleven components, including four sulfur-containing compounds, were identified as characteristic markers distinguishing between non-immersed and sodium sulfite-immersed mung bean sprouts. Esterification and addition reactions were inferred to occur during sodium sulfite immersion, leading to the transformation of flavonoid and saponin sulfates. Commercial samples analysis indicated that sulfur-containing compounds were detectable in 9 of 11 commercial mung bean sprouts. Meanwhile, when sodium sulfite concentration exceeded 3.00 mg/mL and immersion time exceeded 360 min, the contents of total polyphenol and flavonoid were significantly reduced and the antioxidant activity was adversely influenced.PMID:38922905 | DOI:10.1111/1750-3841.17147

FEBS J. 2024 Jun 23. doi: 10.1111/febs.17200. Online ahead of print.ABSTRACTDisorders of Gut-Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large-scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite-host interactions, offering exciting possibilities for the future of treatment of DGBI.PMID:38922780 | DOI:10.1111/febs.17200

Biomed Chromatogr. 2024 Jun 23:e5937. doi: 10.1002/bmc.5937. Online ahead of print.ABSTRACTDexamethasone, a glucocorticoid commonly used in pediatric patients, has potent anti-inflammatory and immunosuppressive properties. However, it is associated with side effects such as reduced lung function and decreased immunity. Pulmonary surfactant lipids are closely linked to lung disease and play a role in reducing surface tension, immune response and antiviral activity. The dysregulation of lipid metabolism is closely associated with lung disease. Hence, untargeted lipidomics may be instrumental in elucidating the effects of dexamethasone on pulmonary surfactant lipids. We obtained surfactant lipid samples from the bronchoalveolar lavage fluid of young mice injected subcutaneously with dexamethasone and conducted a comprehensive lipidomic analysis, comparing them with a control group. We observed a decrease in lipids, such as phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine, and an increase in ceramide, fatty acid, diacylglycerol and monoglyceride, which may impact lung health. This study revealed the influence of dexamethasone on pulmonary surfactant lipids, offering new insights into adverse reactions in clinical settings.PMID:38922717 | DOI:10.1002/bmc.5937

Biomed Chromatogr. 2024 Jun 23:e5932. doi: 10.1002/bmc.5932. Online ahead of print.ABSTRACTAbnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide in epidemiology. Zingiber officinale Roscoe (fresh ginger) has been found to treat diarrhea, but the material basis and mechanism of action that inhibits intestinal peristalsis remain unclear. Metabolomics and serum pharmacology were used to identify differential metabolites, metabolic pathways, and pharmacodynamic substances, and were then combined with network pharmacology to explore the potential targets of ginger that inhibit intestinal peristalsis during diarrhea treatment, and the targets identified were verified using molecular docking and molecular dynamic simulation. We found that 25 active components of ginger (the six most relevant components), 35 potential key targets (three core targets), 40 differential metabolites (four key metabolites), and four major metabolic pathways were involved in the process by which ginger inhibits intestinal peristalsis during diarrhea treatment. This study reveals the complex mechanism of action and pharmacodynamic material basis of ginger in the inhibition of intestinal peristalsis, and this information helps in the development of new Chinese medicine to treat diarrhea and lays the foundation for the clinical application of ginger.PMID:38922712 | DOI:10.1002/bmc.5932

Transgenic Res. 2024 Jun 26. doi: 10.1007/s11248-024-00393-x. Online ahead of print.ABSTRACTPhytoremediation is an environmental safety strategy that might serve as a viable preventative approach to reduce soil contamination in a cost-effective manner. Using plants to remediate pollution from the environment is referred to as phytoremediation. In the past few decades, plants have undergone genetic manipulation to overcome inherent limitations by using genetically modified plants. This review illustrates the eco-friendly process of cleaning the environment using transgenic strategies combined with omics technologies. Herbicides tolerance and phytoremediation abilities have been established in genetically modified plants. Transgenic plants have eliminated the pesticides atrazine and metolachlor from the soil. To expand the application of genetically engineered plants for phytoremediation process, it is essential to test strategies in the field and have contingency planning. Omics techniques were used for understanding various genetic, hormonal, and metabolic pathways responsible for phytoremediation in soil. Transcriptomics and metabolomics provide useful information as resources to understand the mechanisms behind phytoremediation. This review aims to highlight the integration of transgenic strategies and omics technologies to enhance phytoremediation efficiency, emphasizing the need for field testing and comprehensive planning for successful implementation.PMID:38922381 | DOI:10.1007/s11248-024-00393-x

Toxins (Basel). 2024 May 22;16(6):235. doi: 10.3390/toxins16060235.ABSTRACTFusarium verticillioides produces fumonisins, which are mycotoxins inhibiting sphingolipid biosynthesis in humans, animals, and other eukaryotes. Fumonisins are presumed virulence factors of plant pathogens, but may also play a role in interactions between competing fungi. We observed higher resistance to added fumonisin B1 (FB1) in fumonisin-producing Fusarium verticillioides than in nonproducing F. graminearum, and likewise between isolates of Aspergillus and Alternaria differing in production of sphinganine-analog toxins. It has been reported that in F. verticillioides, ceramide synthase encoded in the fumonisin biosynthetic gene cluster is responsible for self-resistance. We reinvestigated the role of FUM17 and FUM18 by generating a double mutant strain in a fum1 background. Nearly unchanged resistance to added FB1 was observed compared to the parental fum1 strain. A recently developed fumonisin-sensitive baker's yeast strain allowed for the testing of candidate ceramide synthases by heterologous expression. The overexpression of the yeast LAC1 gene, but not LAG1, increased fumonisin resistance. High-level resistance was conferred by FUM18, but not by FUM17. Likewise, strong resistance to FB1 was caused by overexpression of the presumed F. verticillioides "housekeeping" ceramide synthases CER1, CER2, and CER3, located outside the fumonisin cluster, indicating that F. verticillioides possesses a redundant set of insensitive targets as a self-resistance mechanism.PMID:38922130 | DOI:10.3390/toxins16060235

Toxics. 2024 May 30;12(6):399. doi: 10.3390/toxics12060399.ABSTRACTPolyvinyl chloride microplastics (PVC-MPs) are microplastic pollutants widely present in the environment, but their potential risks to human lung health and underlying toxicity mechanisms remain unknown. In this study, we systematically analyzed the effects of PVC-MPs on the transcriptome and metabolome of BEAS-2B cells using high-throughput RNA sequencing and untargeted metabolomics technologies. The results showed that exposure to PVC-MPs significantly reduced the viability of BEAS-2B cells, leading to the differential expression of 530 genes and 3768 metabolites. Further bioinformatics analyses showed that PVC-MP exposure influenced the expression of genes associated with fluid shear stress, the MAPK and TGF-β signaling pathways, and the levels of metabolites associated with amino acid metabolism. In particular, integrated pathway analysis showed that lipid metabolic pathways (including glycerophospholipid metabolism, glycerolipid metabolism, and sphingolipid metabolism) were significantly perturbed in BEAS-2B cells following PVC-MPs exposure. This study provides new insights and targets for a deeper understanding of the toxicity mechanism of PVC-MPs and for the prevention and treatment of PVC-MP-associated lung diseases.PMID:38922079 | DOI:10.3390/toxics12060399