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Genes Mar 2024(Burm. f.) Nees is an important medicinal plant known for its bioactive compound andrographolide. NAC transcription factors (NAM, ATAF1/2, and CUC2) play a crucial role...
(Burm. f.) Nees is an important medicinal plant known for its bioactive compound andrographolide. NAC transcription factors (NAM, ATAF1/2, and CUC2) play a crucial role in secondary metabolite production, stress responses, and plant development through hormonal signaling. In this study, a putative partial transcript of three NAC family genes (, and ) was used to isolate full length genes using RACE. Bioinformatics analyses such as protein structure prediction, cis-acting regulatory elements, and gene ontology analysis were performed. Based on in silico predictions, the diterpenoid profiling of the plant's leaves (five-week-old) and the real-time PCR-based expression analysis of isolated NAC genes under abscisic acid (ABA) treatment were performed. Additionally, the expression analysis of isolated NAC genes under MeJA treatment and transient expression in was performed. Full-length sequences of three members of the NAC transcription factor family, (1102 bp), (996 bp), and (1011 bp), were isolated and subjected to the promoter and gene ontology analysis, which indicated their role in transcriptional regulation, DNA binding, ABA-activated signaling, and stress management. It was observed that ABA treatment leads to a higher accumulation of andrographolide and 14-deoxyandrographolide content, along with the upregulation of (9.6-fold) and the downregulation of and in the leaves. With methyl jasmonate treatment, expression decreased, while increased (1.9-fold), with no significant change being observed in . The transient expression of the isolated genes in a heterologous system () demonstrated their functional transcriptional activity, leading to the upregulation of the gene, which is related to the terpene pathway in tobacco. The expression analysis and heterologous expression of and indicated their role in andrographolide biosynthesis.
Topics: Diterpenes; Transcription Factors; Gene Expression Regulation, Plant; Plant Proteins; Andrographis; Nicotiana; Phylogeny; Abscisic Acid; Plant Leaves; Acetates; Cyclopentanes; Oxylipins
PubMed: 38674357
DOI: 10.3390/genes15040422 -
Genes Mar 2024Extensive genome structure variations, such as copy number variations (CNVs) and presence/absence variations, are the basis for the remarkable genetic diversity of...
Extensive genome structure variations, such as copy number variations (CNVs) and presence/absence variations, are the basis for the remarkable genetic diversity of maize; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene leads to increased resistance of maize to herbivory by fall armyworms (FAWs). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of , referred to as . To test whether introgression of the locus into a herbivore-susceptible B73 background that contains a single gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either two, one, or zero copies of the locus in the B73 background via six backcrosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the locus in B73. The resulting B73-2× inbred line displayed increased resistance against FAW, associated with increased expression of , increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×, resulting from the increased JA catabolism. Furthermore, B73-2× displayed reduced water loss in response to drought stress, likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into productive but susceptible crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.
Topics: Zea mays; Animals; DNA Copy Number Variations; Plant Proteins; Lipoxygenase; Herbivory; Oxylipins; Plant Diseases
PubMed: 38674336
DOI: 10.3390/genes15040401 -
Medicina (Kaunas, Lithuania) Mar 2024The incidence and prevalence of cardiac and cerebrovascular diseases are constantly increasing, with chronic coronary syndrome and ischemic stroke as the leading causes... (Review)
Review
The incidence and prevalence of cardiac and cerebrovascular diseases are constantly increasing, with chronic coronary syndrome and ischemic stroke as the leading causes of morbidity and mortality worldwide. According to current knowledge, the heart-brain axis is more than a theoretical concept, with many common pathophysiological mechanisms involved in the onset and evolution of both coronary and cerebral ischemia. Moreover, the focus is on the prevention and early intervention of risk factors in searching for targeted and personalized medical treatment. In this context, this narrative review aims to offer, in a didactic and practice-oriented manner, an up-to-date overview of the role played by lipid-derived biomarkers (from low-density lipoprotein cholesterol to oxylipin and apolipoproteins) in chronic coronary syndrome and ischemic stroke. Firstly, the authors highlight, via relevant epidemiological data, the significant burden of chronic coronary syndrome and ischemic stroke in the general population, thus explaining the need for updated information on this topic. Subsequently, the most important lipid-derived biomarkers and their multiple roles in the pathogenesis of these two disorders are listed. Currently available and experimental targeted therapies based on these lipid-derived biomarkers are presented in the final part of this paper, representing this manuscript's original and novel input.
Topics: Humans; Biomarkers; Ischemic Stroke; Chronic Disease; Lipids; Cholesterol, LDL
PubMed: 38674207
DOI: 10.3390/medicina60040561 -
International Journal of Molecular... Apr 2024As one of the largest and most diverse classes of specialized metabolites in plants, terpenoids (oprenoid compounds, a type of bio-based material) are widely used in the...
As one of the largest and most diverse classes of specialized metabolites in plants, terpenoids (oprenoid compounds, a type of bio-based material) are widely used in the fields of medicine and light chemical products. They are the most important secondary metabolites in coniferous species and play an important role in the defense system of conifers. Terpene synthesis can be promoted by regulating the expressions of terpene synthase genes, and the terpene biosynthesis pathway has basically been clarified in , in which there are multiple rate-limiting enzymes and the rate-limiting steps are difficult to determine, so the terpene synthase gene regulation mechanism has become a hot spot in research. Herein, we amplified a gene (GenBank accession no. MK969119.1) of the MEP pathway (methyl-erythritol 4-phosphate) from . The DXR enzyme activity and chlorophyll a, chlorophyll b and carotenoid contents of overexpressed showed positive regulation. The gene promoter was a tissue-specific promoter and can respond to ABA, MeJA and GA stresses to drive the expression of the reporter gene in . The DXR enzyme was identified as a key rate-limiting enzyme in the MEP pathway and an effective target for terpene synthesis regulation in coniferous species, which can further lay the theoretical foundation for the molecularly assisted selection of high-yielding lipid germplasm of , as well as provide help in the pathogenesis of pine wood nematode disease.
Topics: Abscisic Acid; Acetates; Alkyl and Aryl Transferases; Arabidopsis; Biosynthetic Pathways; Carotenoids; Chlorophyll; Chlorophyll A; Cyclopentanes; Gene Expression Regulation, Plant; Oxylipins; Pinus; Plant Proteins; Plants, Genetically Modified; Promoter Regions, Genetic; Terpenes; Turpentine
PubMed: 38673998
DOI: 10.3390/ijms25084415 -
International Journal of Molecular... Apr 2024Phytophthora root rot is a devastating disease of soybean caused by . However, the resistance mechanism is not yet clear. Our previous studies have shown that enhances...
Phytophthora root rot is a devastating disease of soybean caused by . However, the resistance mechanism is not yet clear. Our previous studies have shown that enhances sensitivity to in soybean, and is downregulated in the transcriptome analysis of -overexpressing transgenic hairy roots. Here, was significantly induced by in susceptible soybean, and the overexpressing of enhanced sensitivity to the pathogen, while silencing enhances resistance to , indicating that is a negative regulator of . Moreover, the jasmonic acid (JA) content and JA synthesis gene was highly upregulated in -silencing roots and highly downregulated in overexpressing ones, suggesting that could respond to through the JA signaling pathway. Furthermore, the expression of several pathogenesis-related genes was significantly lower in -overexpressing roots and higher in -silencing ones. Additionally, we screened and identified the upstream regulator GmbHLH122 and downstream target gene of GmMYB78. GmbHLH122 was highly induced by and could inhibit expression in resistant soybean, and GmMYB78 was highly expressed to activate downstream target gene transcription in susceptible soybean. In conclusion, our data reveal that triggers soybean sensitivity to by inhibiting the JA signaling pathway and the expression of pathogenesis-related genes or through the effects of the GmbHLH122-GmMYB78- cascade pathway.
Topics: Glycine max; Phytophthora; Disease Resistance; Gene Expression Regulation, Plant; Plant Diseases; Plant Proteins; Cyclopentanes; Oxylipins; Transcription Factors; Plants, Genetically Modified; Plant Roots
PubMed: 38673832
DOI: 10.3390/ijms25084247 -
Antioxidants (Basel, Switzerland) Mar 2024Currently, the effects of dietary levels of n-3 highly unsaturated fatty acids (HUFAs) on the growth performance, antioxidant capacity, immunity, and serum oxylipin...
Currently, the effects of dietary levels of n-3 highly unsaturated fatty acids (HUFAs) on the growth performance, antioxidant capacity, immunity, and serum oxylipin profiles of female F-generation Yangtze sturgeon remain unknown. A total of 75 Yangtze sturgeons, an endangered freshwater fish species, with an average body weight of 3.60 ± 0.83 kg, were randomly allocated to 15 concrete pools, with each dietary group represented by 5 fish per pool. The fish were fed five different experimental diets containing various levels of n-3 HUFAs (0.5%, 1.0%, 1.5%, 2.0%, and 2.4%). After a feeding period of 5 months, no significant differences in the growth performances of the fish were observed among the five dietary groups ( > 0.05). However, we did note that the serum levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), and total cholesterol (TCHO) exhibited a marked increase in the fish that consumed higher dietary n-3 HUFA levels ( < 0.05). Conversely, alkaline phosphatase (ALP) activities showed a notable decrease as dietary n-3 HUFA levels increased ( < 0.05). Serum antioxidant indices, such as the activity levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were significantly higher in the 2.4% HUFA group compared to the 0.5% HUFA group. Additionally, muscle antioxidant indices, including total antioxidant capacity (T-AOC), catalase (CAT), and SOD activity, exhibited notable increases as dietary n-3 HUFA levels increased ( < 0.05). Furthermore, there was a decrease in malondialdehyde (MDA) levels as dietary n-3 HUFA levels increased ( < 0.05). In relation to immune indices, only serum immunoglobulin M (IgM) and muscle complement 3 (C3) were found to be influenced by dietary n-3 HUFA levels ( < 0.05). A total of 80 oxylipins were quantified, and our subsequent K-means cluster analysis resulted in the classification of 62 oxylipins into 10 subclasses. Among the different n-3 HUFA diets, a total of 14 differential oxylipins were identified in the sera. These findings demonstrate that dietary supplementation with n-3 HUFAs exceeding a 1.0% level can enhance antioxidant capacity and regulate serum lipid metabolism, potentially through modulation of oxylipins derived from ARA, DHA, and EPA. These insights provide novel perspectives on the mechanisms underlying these observations.
PubMed: 38671869
DOI: 10.3390/antiox13040421 -
Gynecologic Oncology Apr 2024Overweight/obesity is the strongest risk factor for endometrial cancer (EC), and weight management can reduce that risk and improve survival. We aimed to establish the...
OBJECTIVE
Overweight/obesity is the strongest risk factor for endometrial cancer (EC), and weight management can reduce that risk and improve survival. We aimed to establish the differential benefits of intermittent energy restriction (IER) and low-fat diet (LFD), alone and in combination with paclitaxel, to reverse the procancer effects of high-fat diet (HFD)-induced obesity in a mouse model of EC.
METHODS
Lkb1p53 mice were fed HFD or LFD to generate obese and lean phenotypes, respectively. Obese mice were maintained on a HFD or switched to a LFD (HFD-LFD) or IER (HFD-IER). Ten weeks after induction of endometrial cancer, mice in each group received paclitaxel or placebo for 4 weeks. Body and tumor weights; tumoral transcriptomic, metabolomic and oxylipin profiles; and serum metabolic hormones and chemocytokines were assessed.
RESULTS
HFD-IER and HFD-LFD, relative to HFD, reduced body weight; reversed obesity-induced alterations in serum insulin, leptin and inflammatory factors; and decreased tumor incidence and mass, often to levels emulating those associated with continuous LFD. Concurrent paclitaxel, versus placebo, enhanced tumor suppression in each group, with greatest benefit in HFD-IER. The diets produced distinct tumoral gene expression and metabolic profiles, with HFD-IER associated with a more favorable (antitumor) metabolic and inflammatory environment.
CONCLUSION
In Lkb1p53 mice, IER is generally more effective than LFD in promoting weight loss, inhibiting obesity-related endometrial tumor growth (particularly in combination with paclitaxel), and reversing detrimental obesity-related metabolic effects. These findings lay the foundation for further investigations of IER as an EC prevention and treatment strategies in overweight/obesity women.
PubMed: 38669767
DOI: 10.1016/j.ygyno.2024.04.012 -
Metabolites Mar 2024Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported...
Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11-16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention ( < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET ( < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.
PubMed: 38668319
DOI: 10.3390/metabo14040191 -
BioRxiv : the Preprint Server For... Apr 2024Free fatty acid receptor 4 (Ffar4) is a receptor for long-chain fatty acids that attenuates heart failure driven by increased afterload. Recent findings suggest that...
AIMS
Free fatty acid receptor 4 (Ffar4) is a receptor for long-chain fatty acids that attenuates heart failure driven by increased afterload. Recent findings suggest that Ffar4 prevents ischemic injury in brain, liver, and kidney, and therefore, we hypothesized that Ffar4 would also attenuate cardiac ischemic injury.
METHODS AND RESULTS
Using a mouse model of ischemia-reperfusion (I/R), we found that mice with systemic deletion of Ffar4 (Ffar4KO) demonstrated impaired recovery of left ventricular systolic function post-I/R with no effect on initial infarct size. To identify potential mechanistic explanations for the cardioprotective effects of Ffar4, we performed bulk RNAseq to compare the transcriptomes from wild-type (WT) and Ffar4KO infarcted myocardium 3-days post-I/R. In the Ffar4KO infarcted myocardium, gene ontology (GO) analyses revealed augmentation of glycosaminoglycan synthesis, neutrophil activation, cadherin binding, extracellular matrix, rho signaling, and oxylipin synthesis, but impaired glycolytic and fatty acid metabolism, cardiac repolarization, and phosphodiesterase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated impaired AMPK signaling and augmented cellular senescence in the Ffar4KO infarcted myocardium. Interestingly, phosphodiesterase 6c (PDE6c), which degrades cGMP, was the most upregulated gene in the Ffar4KO heart. Further, the soluble guanylyl cyclase stimulator, vericiguat, failed to increase cGMP in Ffar4KO cardiac myocytes, suggesting increased phosphodiesterase activity. Finally, cardiac myocyte-specific overexpression of Ffar4 prevented systolic dysfunction post-I/R, defining a cardioprotective role of Ffa4 in cardiac myocytes.
CONCLUSIONS
Our results demonstrate that Ffar4 in cardiac myocytes attenuates systolic dysfunction post-I/R, potentially by attenuating oxidative stress, preserving mitochondrial function, and modulation of cGMP signaling.
PubMed: 38659901
DOI: 10.1101/2024.04.12.589280 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Apr 2024Sorghum aphid () and head smut fungi () infesting sorghum cause delayed growth and development, and reduce yield and quality. This study use bioinformatics and molecular...
Sorghum aphid () and head smut fungi () infesting sorghum cause delayed growth and development, and reduce yield and quality. This study use bioinformatics and molecular biological approaches to profile the gene expression pattern during sorghum development and under pest infestation, and analyzed the natural allelic DNA variation of sorghum gene family. The findings provide insights for potential application in breeding the stress resistant and high productivity sorghum varieties. The results indicated that there are 28 genes identified in sorghum genome, distributed on 10 chromosomes. The bHLH_MYC_N and HLH domains are the conserved domains of the gene in sorghum. Gene expression analysis showed that . exhibited high expression levels in leaves, showed strong expression in early grains, and . showed high expression levels in mature pollen. In anti-aphid strains at the 5-leaf stage, , . and . were significantly induced in leaves, while . displayed the highest expression level in panicle tissue, which was significantly induced by the infection of head smut. Promoter -element analysis identified methyl jasmonate (MJ), abscisic acid (ABA), salicylic acid (SA) and MYB-binding sites related to drought-stress inducibility. Furthermore, genomic resequencing data analysis revealed natural allelic DNA variations such as single nucleotide polymorphism (SNP) and insertion-deletion (INDEL) for the key . Protein interaction network analysis using STRING indicated that SbAbaIn interacts with TIFYdomain protein, and SbbHLH35.7g interacts with MDR and imporin. exhibited temporal and spatial expression patterns and played vital roles during the sorghum development. Infestation by sugarcane aphids and head smut fungi induced the expression of and ., respectively. modulated the jasmonic acid (JA) pathway to regulate the expression of defensive genes, conferring resistance to insects. On the other hand, . participated in detoxification reactions to defend against pathogens.
Topics: Sorghum; Alleles; Cyclopentanes; Aphids; Oxylipins; Gene Expression Profiling; Animals; Gene Expression Regulation, Plant; Genetic Variation; Genes, myc; Plant Proteins; Plant Diseases; Acetates
PubMed: 38658156
DOI: 10.13345/j.cjb.230641