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MedRxiv : the Preprint Server For... Jun 2024Serum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway...
Serum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway obstruction and poor clinical outcomes in pediatric asthma. Inconsistent patient response to anti-IgE therapies motivates discovery of molecular mechanisms underlying serum IgE level differences in children with asthma. To uncover these mechanisms using complementary metabolomic and transcriptomic data, abundance levels of 529 named metabolites and expression levels of 22,772 genes were measured among children with asthma in the Childhood Asthma Management Program (CAMP, N=564) and the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS, N=309) via the TOPMed initiative. Gene-metabolite associations dependent on IgE were identified within each cohort using multivariate linear models and were interpreted in a biochemical context using network topology, pathway and chemical enrichment, and representation within reactions. A total of 1,617 total IgE-dependent gene-metabolite associations from GACRS and 29,885 from CAMP met significance cutoffs. Of these, glycine and guanidinoacetic acid (GAA) were associated with the most genes in both cohorts, and the associations represented reactions central to glycine, serine, and threonine metabolism and arginine and proline metabolism. Pathway and chemical enrichment analysis further highlighted additional related pathways of interest. The results of this study suggest that GAA may modulate total IgE levels in two independent pediatric asthma cohorts with different characteristics, supporting the use of L-Arginine as a potential therapeutic for asthma exacerbation. Other potentially new targetable pathways are also uncovered.
PubMed: 38883716
DOI: 10.1101/2024.06.05.24308502 -
Heliyon Jun 2024Drought stress poses a significant threat to (L.), impacting its growth, yield, and profitability. This study investigates the effects of foliar application of...
Drought stress poses a significant threat to (L.), impacting its growth, yield, and profitability. This study investigates the effects of foliar application of individual and interactive pharmaceutical (Paracetamol; 0 and 250 mg L) and amino acid (0 and 4 ml/L) on the growth, physiology, and yield of under drought stress. Seedlings were subjected to varying levels of drought stress (100% field capacity (FC; control) and 50% FC). Sole amino acid application significantly improved chlorophyll content, proline content, and relative water contents, as well as the activities of antioxidative enzymes (such as superoxide dismutase and catalase) while potentially decreased malondialdehyde and hydrogen peroxide contents under drought stress conditions. Pearson correlation analysis revealed strong positive correlations between these parameters and seed yield (R = 0.8-1), indicating their potential to enhance seed yield. On the contrary, sole application of paracetamol exhibited toxic effects on seedling growth and physiological aspects of . Furthermore, the combined application of paracetamol and amino acids disrupted physio-biochemical functions, leading to reduced yield. Overall, sole application of amino acids proves to be more effective in ameliorating the negative effects of drought on
PubMed: 38882271
DOI: 10.1016/j.heliyon.2024.e31544 -
Synthetic and Systems Biotechnology Dec 2024Acetic acid is a common inhibitor present in lignocellulose hydrolysate, which inhibits the ethanol production by yeast strains. Therefore, the cellulosic ethanol...
Acetic acid is a common inhibitor present in lignocellulose hydrolysate, which inhibits the ethanol production by yeast strains. Therefore, the cellulosic ethanol industry requires yeast strains that can tolerate acetic acid stress. Here we demonstrate that overexpressing a yeast native arginase-encoding gene, , renders acetic acid tolerance. Specifically, ethanol yield increased by 27.3% in the -overexpressing strain compared to the control strain under 5.0 g/L acetic acid stress. The global intracellular amino acid level and compositions were further analyzed, and we found that overexpression reduced the total amino acid content in response to acetic acid stress. Moreover, the overexpressing strain showed increased ATP level and improved cell membrane integrity. Notably, we demonstrated that the effect of overexpression was independent of the spermidine and proline metabolism, which indicates novel mechanisms for enhancing yeast stress tolerance. Our studies also suggest that is a novel genetic element to be used in synthetic biology of yeast for efficient production of fuel ethanol.
PubMed: 38882181
DOI: 10.1016/j.synbio.2024.05.013 -
Drug Design, Development and Therapy 2024The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This...
PURPOSE
The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics.
METHODS
First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters.
RESULTS
BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment.
CONCLUSION
BDD can effectively improve anxiety-like behaviors by regulating the gut-brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters.
Topics: Animals; Rats; Anti-Anxiety Agents; Drugs, Chinese Herbal; Male; Metabolomics; Disease Models, Animal; Rats, Sprague-Dawley; Gastrointestinal Microbiome; Stress, Psychological; Anxiety; Restraint, Physical; Hippocampus
PubMed: 38882046
DOI: 10.2147/DDDT.S458983 -
Translational Cancer Research May 2024Proline dehydrogenase () encodes a mitochondrial protein that catalyzes the first step of proline degradation and is related to angiogenesis. Angiogenesis is a critical...
BACKGROUND
Proline dehydrogenase () encodes a mitochondrial protein that catalyzes the first step of proline degradation and is related to angiogenesis. Angiogenesis is a critical process in the development and progression of tumors, including lung adenocarcinoma (LUAD), as tumor growth and metastasis are dependent on angiogenesis. The mitochondria and their associated genes thus play a vital role in tumor therapy. However, the specific mechanism of action of in LUAD is not yet clear. The aim of this study was thus to clarify the specific mechanism of as a mitochondrial gene in LUAD.
METHODS
This study identified genes related to mitochondria and angiogenesis in LUAD. Based on the high and low expression of the genes in LUAD, we grouped them and conducted relevant bioinformatics analysis on the differentially expressed genes.
RESULTS
We screened genes related to mitochondria and angiogenesis in the differential genes of LUAD, and identified as a gene of interest. The expression of was associated with the survival outcome of patients with LUAD. Additionally, was found to be associated with immune cell infiltration and tumor mutations.
CONCLUSIONS
Mitochondrial metabolism and angiogenesis may have significant therapeutic ramifications for patients with LUAD. We identified , a gene exerts a dual role in cancer. PRODH may be a prospective therapeutic target in LUAD and a possible diagnostic and prognostic biomarker associated with immune infiltration and tumor mutational burden.
PubMed: 38881931
DOI: 10.21037/tcr-23-2109 -
Frontiers in Microbiology 2024Salt stress is a major abiotic stress that affects the growth of and many psammophytes in the desert areas of Northwest China. However, various Plant Growth-Promoting...
Salt stress is a major abiotic stress that affects the growth of and many psammophytes in the desert areas of Northwest China. However, various Plant Growth-Promoting Rhizobacteria (PGPR) have been known to play an important role in promoting plant growth and alleviating the damaging effects of salt stress. In this study, three PGPR strains belonging to were isolated from the rhizosphere of by morphological and molecular identification. All isolated strains exhibited capabilities of producing IAA, solubilizing phosphate, and fixing nitrogen, and were able to tolerate high levels of NaCl stress, up to 8-12%. The results of the pot-based experiment showed that salt (400 mM NaCl) stress inhibited seedlings' growth performance as well as biomass production, but after inoculation with strains P2, S37, and S40, the plant's height significantly increased by 26.87, 17.59, and 13.36%, respectively (), and both aboveground and root fresh weight significantly increased by more than 2 times compared to NaCl treatment. Additionally, inoculation with P2, S37, and S40 strains increased the content of photosynthetic pigments, proline, and soluble protein in seedlings under NaCl stress, while reducing the content of malondialdehyde and soluble sugars. Metabolomic analysis showed that strain S40 induces seedling leaves metabolome reprogramming to regulate cell metabolism, including plant hormone signal transduction and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. Under NaCl stress, inoculation with strain S40 upregulated differential metabolites in plant hormone signal transduction pathways including plant hormones such as auxins (IAA), cytokinins, and jasmonic acid. The results indicate that inoculation with can promote the growth of seedlings under NaCl stress and enhance salt tolerance by increasing the content of photosynthetic pigments, accumulating osmoregulatory substances, regulating plant hormone levels This study contributes to the enrichment of PGPR strains capable of promoting the growth of desert plants and has significant implications for the psammophytes growth and development in desert regions, as well as the effective utilization and transformation of saline-alkali lands.
PubMed: 38881656
DOI: 10.3389/fmicb.2024.1408622 -
BMC Plant Biology Jun 2024Cadmium (Cd) is a nonessential element in plants and has adverse effects on the growth and development of plants. However, the molecular mechanisms of Cd phytotoxicity,...
Cadmium (Cd) is a nonessential element in plants and has adverse effects on the growth and development of plants. However, the molecular mechanisms of Cd phytotoxicity, tolerance and accumulation in hyperaccumulators Solanum nigrum L. has not been well understood. Here, physiology, transcriptome, and metabolome analyses were conducted to investigate the influence on the S. nigrum under 0, 25, 50, 75 and 100 µM Cd concentrations for 7 days. Pot experiments demonstrated that compared with the control, Cd treatment significantly inhibited the biomass, promoted the Cd accumulation and translocation, and disturbed the balance of mineral nutrient metabolism in S. nigrum, particularly at 100 µM Cd level. Moreover, the photosynthetic pigments contents were severely decreased, while the content of total protein, proline, malondialdehyde (MDA), HO, and antioxidant enzyme activities generally increased first and then slightly declined with increasing Cd concentrations, in both leaves and roots. Furthermore, combined with the previous transcriptomic data, numerous crucial coding-genes related to mineral nutrients and Cd ion transport, and the antioxidant enzymes biosynthesis were identified, and their expression pattern was regulated under different Cd stress. Simultaneously, metabolomic analyses revealed that Cd treatment significantly changed the expression level of many metabolites related to amino acid, lipid, carbohydrate, and nucleotide metabolism. Metabolic pathway analysis also showed that S. nigrum roots activated some differentially expressed metabolites (DEMs) involved in energy metabolism, which may enhance the energy supply for detoxification. Importantly, central common metabolism pathways of DEGs and DEMs, including the "TCA cycle", "glutathione metabolic pathway" and "glyoxylate and dicarboxylate metabolism" were screened using conjoint transcriptomics and metabolomics analysis. Our results provide some novel evidences on the physiological and molecular mechanisms of Cd tolerance in hyperaccumulator S. nigrum plants.
Topics: Solanum nigrum; Cadmium; Transcriptome; Metabolome; Metabolomics; Gene Expression Regulation, Plant; Stress, Physiological; Plant Leaves; Plant Roots
PubMed: 38880885
DOI: 10.1186/s12870-024-05278-z -
BMC Plant Biology Jun 2024In the course of their life, plants face a multitude of environmental anomaly that affects their growth and production. In recent decades, lead (Pb) gained an increasing...
In the course of their life, plants face a multitude of environmental anomaly that affects their growth and production. In recent decades, lead (Pb) gained an increasing attention as it is among the most significant contaminants in the environment. Therefore, in this study the effects of Pb concentrations (0, 50 and 100 ppm) on Vicia faba plants and attempts to alleviate this stress using chitosan (Chs; 0 and 0.1%) were performed. The results validated that with increasing Pb concentrations, a decline in growth, pigments and protein contents was observed. In the same time, a significant upsurge in the stress markers, both malondialdehyde (MDA) and HO, was observed under Pb stress. Nonetheless, foliar spraying with Chs improves the faba bean growth, pigment fractions, protein, carbohydrates, reduces MDA and HO contents and decreases Pb concentrations under Pb stress. Pb mitigation effects by Chs are probably related with the activity of antioxidant enzymes, phenylalanine ammonia lyase (PAL) and proline. The application of Chs enhanced the activities of peroxidase, catalase and PAL by 25.77, 17.71 and 20.07%, respectively at 100 ppm Pb compared to their control. Plant genomic material exhibits significant molecular polymorphism, with an average polymorphism of 91.66% across all primers. To assess the genetic distance created among treatments, the dendrogram was constructed and the results of the similarity index ranged from 0.75 to 0.95, indicating genetic divergence. Our research offers a thorough comprehension of the role of Chs in lessening the oxidative stress, which will encourage the use of Chs in agricultural plant protection.
Topics: Vicia faba; Lead; Oxidative Stress; Chitosan; Hydrogen Peroxide; Malondialdehyde; Antioxidants; Plant Leaves; Plant Proteins; Phenylalanine Ammonia-Lyase
PubMed: 38877427
DOI: 10.1186/s12870-024-05227-w -
BMC Plant Biology Jun 2024The generation of new eggplant (Solanum melongena L.) cultivars with drought tolerance is a main challenge in the current context of climate change. In this study, the...
BACKGROUND
The generation of new eggplant (Solanum melongena L.) cultivars with drought tolerance is a main challenge in the current context of climate change. In this study, the eight parents (seven of S. melongena and one of the wild relative S. incanum L.) of the first eggplant MAGIC (Multiparent Advanced Generation Intercrossing) population, together with four F hybrids amongst them, five S5 MAGIC recombinant inbred lines selected for their genetic diversity, and one commercial hybrid were evaluated in young plant stage under water stress conditions (30% field capacity; FC) and control conditions (100% FC). After a 21-day treatment period, growth and biomass traits, photosynthetic pigments, oxidative stress markers, antioxidant compounds, and proline content were evaluated.
RESULTS
Significant effects (p < 0.05) were observed for genotype, water treatments and their interaction in most of the traits analyzed. The eight MAGIC population parental genotypes displayed a wide variation in their responses to water stress, with some of them exhibiting enhanced root development and reduced foliar biomass. The commercial hybrid had greater aerial growth compared to root growth. The four F hybrids among MAGIC parents differed in their performance, with some having significant positive or negative heterosis in several traits. The subset of five MAGIC lines displayed a wide diversity in their response to water stress.
CONCLUSION
The results show that a large diversity for tolerance to drought is available among the eggplant MAGIC materials, which can contribute to developing drought-tolerant eggplant cultivars.
Topics: Solanum melongena; Antioxidants; Dehydration; Hybridization, Genetic; Genotype; Droughts; Hybrid Vigor; Proline; Biomass
PubMed: 38877388
DOI: 10.1186/s12870-024-05235-w -
Ecotoxicology and Environmental Safety Jul 2024Selenium (Se), as a vital stress ameliorant, possesses a beneficial effect on mediating detrimental effects of environmental threats. However, the mechanisms of Se in...
Selenium (Se), as a vital stress ameliorant, possesses a beneficial effect on mediating detrimental effects of environmental threats. However, the mechanisms of Se in mitigating the deleterious effects of drought are still poorly understood. Gentiana macrophylla Pall. is a well-known Chinese medicinal herb, and its root, as the main medicinal site, has significant therapeutic effects. The purpose of this experiment was to investigate the functions of Se on the seedling growth and physiobiochemical characteristics in G. macrophylla subjected to drought stress. The changes in microstructure and chloroplast ultrastructure of G. macrophylla leaves under drought exposure were characterized by scanning electron microscopy (SEM), scanning electron microscopes and energy dispersive X-Ray spectroscope (SEM-EDX), and transmission electron microscopy (TEM), respectively. Results revealed that drought stress induced a notable increase in oxidative toxicity in G. macrophylla, as evidenced by elevated levels of hydrogen peroxide (HO), lipid peroxidation (MDA), enhanced antioxidative response, decreased plant photosynthetic function, and inhibited plant growth. Chloroplasts integrity with damaged membranes and excess osmiophilic granule were observed in the drought-stressed plants. Se supplementation notably recovered the stomatal morphology, anatomical structure damage, and chloroplast ultrastructure of G. macrophylla leaves caused by drought exposure. Exogenous Se application markedly enhanced SPAD, photosynthetic stomatal exchange parameters, and photosystem II activity. Se supplementation significantly promoted the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT), while reducing levels of MDA, superoxide anion (O) and HO, and improving membrane integrity. Furthermore, the ameliorative effects of Se were also suggested by increased contents of osmotic substances (soluble sugar and proline), boosted content of gentiopicroside and loganinic acid in roots, and alleviated the inhibition in plant growth and biomass. Fourier transform infrared (FTIR) analysis of Se-treated G. macrophylla roots under drought stress demonstrated that Se-stimulated metabolites including O-H, C-H, N-H, C-N, and CO functional groups, were involved in resisting drought stress. Correlation analysis indicated an obvious negative correlation between growth parameters and MDA, O and HO content, while a positive correlation with photosynthetic gas exchange parameters. Principal component analysis (PCA) results explained the total variance into two principal components contributing the maximum (93.50 %) among the drought exposure with or without Se due to the various experiment indexes. In conclusion, Se exerts beneficial properties on drought-induced detrimental effects in G. macrophylla by relieving oxidative stress, improving photosynthesis indexes, PSII activity, regulating anatomical changes, altering levels of gentiopicroside and loganinic acid, and promoting growth of drought-stressed G. macrophylla.
Topics: Gentiana; Selenium; Droughts; Plant Leaves; Photosynthesis; Stress, Physiological; Chloroplasts; Lipid Peroxidation; Hydrogen Peroxide; Oxidative Stress; Seedlings; Antioxidants; Plant Roots
PubMed: 38875819
DOI: 10.1016/j.ecoenv.2024.116591