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Background: Both genetic background and diet are important determinants of cardiovascular diseases (CVD). Understanding gene-diet interactions could help improve CVD prevention and prognosis. We aimed to summarise the evidence on gene-diet interactions and CVD outcomes systematically.Methods: We searched MEDLINE® via Ovid, Embase, PubMed®, and The Cochrane Library for relevant studies published until June 6th 2022. We considered for inclusion cross-sectional, case-control, prospective cohort, nested case-control, and case-cohort studies as well as randomised controlled trials that evaluated the interaction between genetic variants and/or genetic risk scores and food or diet intake on the risk of related outcomes, including myocardial infarction, coronary heart disease (CHD), stroke and CVD as a composite outcome. The PROSPERO protocol registration code is CRD42019147031.Results and Discussion: We included 59 articles based on data from 29 studies; six articles involved multiple studies, and seven did not report details of their source population. The median sample size of the articles was 2562 participants. Of the 59 articles, 21 (35.6%) were qualified as high quality, while the rest were intermediate or poor. Eleven (18.6%) articles adjusted for multiple comparisons, four (7.0%) attempted to replicate the findings, 18 (30.5%) were based on Han-Chinese ethnicity, and 29 (49.2%) did not present Minor Allele Frequency. Fifty different dietary exposures and 52 different genetic factors were investigated, with alcohol intake and ADH1C variants being the most examined. Of 266 investigated diet-gene interaction tests, 50 (18.8%) were statistically significant, including CETP-TaqIB and ADH1C variants, which interacted with alcohol intake on CHD risk. However, interactions effects were significant only in some articles and did not agree on the direction of effects. Moreover, most of the studies that reported significant interactions lacked replication. Overall, the evidence on gene-diet interactions on CVD is limited, and lack correction for multiple testing, replication and sample size consideration. [ABSTRACT FROM AUTHOR]

Anti-interleukin (IL)-1 agents have been developed for the treatment of autoinflammatory and rheumatic conditions, where overproduction of IL-1 is an important pathophysiologic process. IL-1α and IL-1β are the most studied members of the IL-1 family of cytokines and have the strongest proinflammatory effects. A naturally occurring antagonist (IL-1Ra) mitigates their proinflammatory effects. Overproduction of both IL-1α (released by inflamed/damaged pericardial cells) and IL-1β (released by inflammatory cells) is now a well-recognized therapeutic target in patients with recurrent idiopathic pericarditis. Currently, there are three available anti-IL-1 agents: anakinra (recombinant human IL-1Ra), rilonacept (a soluble decoy receptor 'trap', binding both IL-1α and IL-1β), and canakinumab (human monoclonal anti-IL-1β antibody). For patients with corticosteroid-dependent and colchicine-resistant recurrent pericarditis with evidence of systemic inflammation, as evidenced by elevated C-reactive protein, the efficacy and safety of anakinra (2 mg/kg/day up to 100 mg/day subcutaneously usually for at least 6 months, then tapered) and rilonacept (320 mg subcutaneously for the first day followed by 160 mg subcutaneously weekly) have been clearly demonstrated in observational studies and randomized controlled clinical trials. Severe side effects are rare and discontinuation rates are very low (<4%). The most common reported side effect is injection site reactions (>50% of patients). In this article, we describe the historical and pathophysiological background and provide a comprehensive review of these agents, which appear to be the most significant advance in medical therapy of recurrent pericarditis in the last 5 years. [ABSTRACT FROM AUTHOR]

We subjected the components of the glycolysis and energy metabolism pathways of Rhodobacter sphaeroides (R. sphaeroides) to metabolic engineering to improve the titer and yield of coenzyme Q10 (CoQ10). Phosphofructokinase (PFK), cyclic adenylate-dependent protein kinase (PKAC), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and adenosine triphosphate hydrolase (KdpC) were overexpressed in R. sphaeroides VK-2-3 (VK-2-3). The strains were labeled R. sphaeroides PFK (RS.PFK), RS.PKAC, RS.PFK-PKAC, RS.KdpC, RS.GAPDH, and RS.KdpC-GAPDH. Results showed that the CoQ10 titers of RS.PFK, RS.PKAC, and RS.PFK-PKAC were 300.96 ± 0.87, 405.94 ± 4.77, and 379.94 ± 0.42 mg/l, respectively. The CoQ10 titers of RS.PFK and VK-2-3 were not significantly different; however, those for RS.PKAC and RS.PFK-PKAC were 13 and 6% higher than that of VK-2-3, respectively. Further, the titers of RS.KdpC, RS.GAPDH, and RS.KdpC-GAPDH were 360.17 ± 0.39, 409.79 ± 0.76, and 359.87 ± 1.14 mg/l, respectively. The titers of RS.KdpC and RS.KdpC-GAPDH were not significantly different from that for VK-2-3, whereas that for RS.GAPDH was 14% higher than that of VK-2-3. Finally, when the cultures of RS.GAPDH and VK-2-3 were scaled up in 5-L fermenters, the CoQ10 titers and RS.GAPDH yields increased by 44.3 and 37.8%, respectively, compared with VK-2-3. To the best of our knowledge, the glycolysis pathway of R. sphaeroides was studied for the first time in this study. We genetically modified the components of the energy metabolism pathway to obtain the strain with high yield of CoQ10 mutant RS.GAPDH. The findings of this study can serve as a basis for future studies involving metabolic engineering of CoQ10-producing strains. [ABSTRACT FROM AUTHOR]

While plants are an abundant source of valuable natural products, it is often challenging to produce those products for commercial application. Often organic synthesis is too expensive for a viable commercial product and the biosynthetic pathways are often so complex that transferring them to a microorganism is not trivial or feasible. For plants not suited to agricultural production of natural products, hairy root cultures offer an attractive option for a production platform which offers genetic and biochemical stability, fast growth, and a hormone free culture media. Advances in metabolic engineering and synthetic biology tools to engineer hairy roots along with bioreactor technology is to a point where commercial application of the technology will soon be realized. We discuss different applications of hairy roots. We also use a case study of the advancements in understanding of the terpenoid indole alkaloid pathway in Catharanthus roseus hairy roots to illustrate the advancements and challenges in pathway discovery and in pathway engineering. [ABSTRACT FROM AUTHOR]

Ganoderma lucidum is an important medicinal fungus in Asian countries. Ganoderic acid (GA) is the major variety of bioactive and medicative components in G. lucidum. Biosynthesis of secondary metabolites is usually associated with cell differentiation and development. However, the mechanism underlying these phenomena remain unclear. Transcription factors play an essential regulatory role in the signal transduction pathway, owing to the fact that they represent the major link between signal transduction and expression of target genes. In the present study, we performed transcriptome and metabolome analyses to identify transcription factors involved in GA biosynthesis during development of G. lucidum. Transcriptome data revealed differentially expressed genes between mycelia and primordia, as well as between mycelia and the fruiting body. Results from gene ontology enrichment analysis and metabolome analyses suggested that GAs and flavonoids biosynthetic process significantly changed during fungal development. The analysis of predicted occurrences of DNA-binding domains revealed a set of 53 potential transcription factor families in G. lucidum. Notably, we found homeobox transcription factor and velvet family protein played important role in GA biosynthesis. Combined with previous studies, we provided a model diagram of transcription factors involved in GA biosynthesis during fruiting body formation. Collectively, these results are expected to enhance our understanding into the mechanisms underlying secondary metabolite biosynthesis and development in fungi. [ABSTRACT FROM AUTHOR]

The Oliveria decumbens Vent. is a wild, rare, annual medicinal plant and endemic plant of Iran that has metabolites (mostly terpenes) which make it a precious plant in Persian Traditional Medicine and also a potential chemotherapeutic agent. The lack of genetic resources has slowed the discovery of genes involved in the terpenes biosynthesis pathway. It is a wild relative of Daucus carota. In this research, we performed the transcriptomic differences between two samples, flower and root of Oliveria decumbens, and also analyze the expression value of the genes involved in terpenoid biosynthesis by RNA-seq and its essential oil's phytochemicals analyzed by GC/MS. In total, 136,031,188 reads from two samples of flower and root have been produced. The result shows that the MEP pathway is mostly active in the flower and the MVA in the root. Three genes of GPP, FPPS, and GGPP that are the precursors in the synthesis of mono, di, and triterpenes are upregulated in root and 23 key genes were identified that are involved in the biosynthesis of terpenes. Three genes had the highest upregulation in the root including, and on the other hand, another three genes had the expression only in the flower. Meanwhile, 191 and 185 upregulated genes in the flower and root of the plant, respectively, were selected for the gene ontology analysis and reconstruction of co-expression networks. The current research is the first of its kind on Oliveria decumbens transcriptome and discussed 67 genes that have been deposited into the NCBI database. Collectively, the information obtained in this study unveils the new insights into characterizing the genetic blueprint of Oliveria decumbens Vent. which paved the way for medical/plant biotechnology and the pharmaceutical industry in the future. [ABSTRACT FROM AUTHOR]

DNA damage induces the activation of many different signals associated with repair or cell death, but it is also connected with physiological events, such as adult neurogenesis and B-cell differentiation. DNA damage induces different signaling pathways, some of them linked to important metabolic changes. The mTORC1 pathway has a central role in the regulation of growth processes and cell division in response to environmental changes and also controls protein synthesis, lipid biogenesis, nucleotide synthesis, and expression of glycolytic genes. Here, we report that double-strand breaks induced with etoposide affect the expression of genes encoding different enzymes associated with specific metabolic pathways in Ramos cells. We also analyzed the role of mTOR signaling, demonstrating that doublestrand breaks induce downregulation of mTOR signaling. Specific inhibition of mTORC1 using rapamycin also induced changes in the expression of metabolic genes. Finally, we demonstrated that DNA damage and rapamycin can regulate glucose uptake. In summary, our findings show that etoposide and rapamycin affect the expression of metabolic genes as well as apoptotic and proliferation markers in Ramos cells, increasing our understanding of cancer metabolism. [ABSTRACT FROM AUTHOR]

The prevalence of non-alcoholic steatohepatitis (NASH) is rapidly increasing and associated with cardiovascular disease (CVD), the major cause of mortality in NASH patients. Although sharing common risk factors, the mechanisms by which NASH may directly contribute to the development to CVD remain poorly understood. The aim of this study is to gain insight into key molecular processes of NASH that drive atherosclerosis development. Thereto, a time-course study was performed in Ldlr−/−.Leiden mice fed a high-fat diet to induce NASH and atherosclerosis. The effects on NASH and atherosclerosis were assessed and transcriptome analysis was performed. Ldlr−/−.Leiden mice developed obesity, hyperlipidemia and insulin resistance, with steatosis and hepatic inflammation preceding atherosclerosis development. Transcriptome analysis revealed a time-dependent increase in pathways related to NASH and fibrosis followed by an increase in pro-atherogenic processes in the aorta. Gene regulatory network analysis identified specific liver regulators related to lipid metabolism (SC5D, LCAT and HMGCR), inflammation (IL1A) and fibrosis (PDGF, COL3A1), linked to a set of aorta target genes related to vascular inflammation (TNFA) and atherosclerosis signaling (CCL2 and FDFT1). The present study reveals pathogenic liver processes that precede atherosclerosis development and identifies hepatic key regulators driving the atherogenic pathways and regulators in the aorta. [ABSTRACT FROM AUTHOR]

Nepeta tenuifolia is a medicinal plant rich in terpenoids and flavonoids with antiviral, immunoregulatory, and anti-inflammatory activities. The peltate glandular trichome (PGT) is a multicellular structure considered to be the primary storage organ for monoterpenes; it may serve as an ideal model for studying cell differentiation and the development of glandular trichomes (GTs). The genes that regulate the development of GTs have not yet been well studied. In this study, we identified NtMIXTA1, a GT development-associated gene from the R2R3 MYB SBG9 family. NtMIXTA1 overexpression in tobacco resulted in the production of longer and denser GTs. Virus-induced gene silencing of NtMIXTA1 resulted in lower PGT density, a significant reduction in monoterpene concentration, and the decreased expression of genes related to monoterpene biosynthesis. Comparative transcriptome and widely targeted metabolic analyses revealed that silencing NtMIXTA1 significantly influenced the expression of genes, and the production of metabolites involved in the biosynthesis of terpenoids, flavonoids, and lipids. This study provides a solid foundation describing a mechanism underlying the regulation of GT development. In addition, this study further deepens our understanding of the regulatory networks involved in GT development and GT development-associated metabolite flux, as well as provides valuable reference data for studying plants with a high medicinal value without genetic transformation. [ABSTRACT FROM AUTHOR]

As the largest group of structurally diverse metabolites, terpenoids are versatile natural compounds that act as metabolism mediators, plant volatiles, and ecological communicators. However, few terpenoid compounds have been identified in plant parts of sacred lotus (Nelumbo nucifera Gaertn.). To elucidate the molecular genetic basis of the terpene biosynthetic pathway, terpenes from different parts of the plant, including seeds (S), young leaves (YL), mature leaves (ML), white flowers (WF), yellow flowers (YF), and red flowers (RF), were identified by LC-MS/MS and the relative contents of the same terpenes in different parts were compared. The results indicate that all plant parts primarily consist of triterpenes, with only minor quantities of sesquiterpenes and diterpenes, and there were differences in the terpene content detected in different plant parts. To illustrate the biosynthesis of various terpenoids, RNA sequencing was performed to profile the transcriptomes of various plant parts, which generated a total of 126.95 GB clean data and assembled into 29,630 unigenes. Among these unigenes, 105 candidate unigenes are involved in the mevalonate (MVA) pathway, methyl-erythritol phosphate (MEP) pathway, terpenoid backbone biosynthesis pathway, and terpenoid synthases pathway. Moreover, the co-expression network between terpene synthase (TPS) and WRKY transcription factors provides new information for the terpene biosynthesis pathway. [ABSTRACT FROM AUTHOR]

Bioactive lipid molecules have been proposed to play important roles linking obesity/metabolic syndrome and cancers. Studies reveal that aberrant lipid metabolic signaling can reprogram cancer cells and non-cancer cells in the tumor microenvironment, contributing to cancer initiation, progression, metastasis, recurrence, and poor therapeutic response. Existing evidence indicates that controlling lipid metabolism can be a potential strategy for cancer prevention and therapy. By reviewing the current literature on the lipid metabolism in various cancers, we summarized major lipid molecules including fatty acids and cholesterol as well as lipid droplets and discussed their critical roles in cancer cells and non-cancer in terms of either promoting- or anti-tumorigenesis. This review provides an overview of the lipid molecules in cellular entities and their tumor microenvironment, adding to the existing knowledge with lipid metabolic reprogramming in immune cells and cancer associated cells. Comprehensive understanding of the regulatory role of lipid metabolism in cellular entities and their tumor microenvironment will provide a new direction for further studies, in a shift away from conventional cancer research. Exploring the lipid-related signaling targets that drive or block cancer development may lead to development of novel anti-cancer strategies distinct from traditional approaches for cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

Cinnamomum camphora (L.) Presl essential oil (CCEO) is a volatile oil with aroma and is extracted from various tissues of Cinnamomumcamphora. It is traditionally used as a spice, preservative, as an anti-inflammatory and for sterilization. Terpenoids are the main active components in CCEO. Based on currently available research, considerable effort is still needed to study the biosynthesis and regulation of terpenoids in CCEO. In this review, the research progress related to terpenoid biosynthesis and bioactivity in CCEO in recent years is summarized, with the data compiled and presented mainly from online resources such as PubMed, Scopus and CNKI in China up to May 2022. The research advances related to key enzymes in the terpenoid biosynthesis pathway are mainly discussed. Previous studies have isolated some genes encoding key enzymes involved in terpenoid biosynthesis; however, among these genes, only a few TPS genes have been verified to catalyze the production of terpenoid synthases at the protein level. Most genes encoding key enzymes have been cloned and isolated, but no transgenic experiments have been carried out to verify gene function. In-depth study of the biosynthesis of terpenoids in CCEO may contribute to a better understanding of the differential accumulation of terpenoids in different types of C. camphora and provide reference for improving terpenoid content in CCEO. [ABSTRACT FROM AUTHOR]

Background: The central nervous system (CNS) is enriched in lipids; despite this, studies exploring the functional roles of lipids in the brain are still limited. Sterol regulatory element binding protein (SREBP) signaling is a transcriptomic pathway that predominantly participates in the maintenance of lipid homeostasis; however, its involvement in the CNS dysfunction is not well-established. In this study, we aimed to characterize and pinpoint specific genes of the SREBP pathway which may be implicated in neurodegenerative, neurological, and neuropsychiatric diseases. Methods: In silico bioinformatic analysis was performed using the open-source databases DisGeNET and MSigDB. Protein-protein interaction data were visualized and analyzed using STRING, after which GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were conducted via DAVID (Database for Annotation, Visualization and Integrated Discovery). Results: Several common genes were identified between the SREBP pathway and CNS disorders. In GO enrichment analysis, the most enriched biological processes included lipid, cholesterol, and steroid biosynthetic processes; the most enriched molecular functions were transcription factor-related; and the most enriched subcellular compartments revealed that the genes involved in CNS disorders were mainly associated with the enzyme complexes of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). In KEGG enrichment analysis, the most enriched pathway was the AMP-activated protein kinase (AMPK) signaling pathway, and the top-ranked genes significantly enriched under this pathway were ACACA, ACACB, FASN, HMGCR, MTOR, PPARGC1A, PRKAA1, SCD, SIRT1, and SREBF1. Conclusions: The findings of this study strengthen the evidence linking the involvement of lipid homeostasis in CNS functions. We suggest herein the roles of downstream ACC and FASN enzymes and upstream AMPK signaling in the SREBP pathway as mechanisms underlying neurodegenerative, neurological, and neuropsychiatric CNS disorders. [ABSTRACT FROM AUTHOR]

Peroxisomes participate in several important metabolic processes in eukaryotic cells, such as the detoxification of reactive oxygen species (ROS) or the degradation of fatty acids by β-oxidation. Recently, the presence of peroxisomes in the cryptophyte Guillardia theta and other "chromalveolates" was revealed by identifying proteins for peroxisomal biogenesis. Here, we investigated the subcellular localization of candidate proteins of G. theta in the diatom Phaeodactylum tricornutum , either possessing a putative peroxisomal targeting signal type 1 (PTS1) sequence or factors lacking a peroxisomal targeting signal but known to be involved in β-oxidation. Our results indicate important contributions of the peroxisomes of G. theta to the carbohydrate, ether phospholipid, nucleotide, vitamin K, ROS, amino acid, and amine metabolisms. Moreover, our results suggest that in contrast to many other organisms, the peroxisomes of G. theta are not involved in the β-oxidation of fatty acids, which exclusively seems to occur in the cryptophyte's mitochondria. [ABSTRACT FROM AUTHOR]

The sesquiterpenoid hormone juvenile hormone (JH) controls development, reproduction, and metamorphosis in insects, and has long been thought to be confined to the Insecta. While it remains true that juvenile hormone is specifically synthesized in insects, other types or forms of sesquiterpenoids have also been discovered in distantly related animals, such as the jellyfish. Here, we combine the latest literature and annotate the sesquiterpenoid biosynthetic pathway genes in different animal genomes. We hypothesize that the sesquiterpenoid hormonal system is an ancestral system established in an animal ancestor and remains widespread in many animals. Different animal lineages have adapted different enzymatic routes from a common pathway, with cnidarians producing farnesoic acid (FA); non-insect protostomes and non-vertebrate deuterostomes such as cephalochordate and echinoderm synthesizing FA and methyl farnesoate (MF); and insects producing FA, MF, and JH. Our hypothesis revolutionizes the current view on the sesquiterpenoids in the metazoans, and forms a foundation for a re-investigation of the roles of this important and yet neglected type of hormone in different animals. [ABSTRACT FROM AUTHOR]

Root size is a key trait in plant cultivation and can be influenced by the cultivation environment. However, physical evidence of root size change in a secular context is scarce due to the difficulty in preserving ancient root samples, and how they were modified during the domestication and cultivation stays unclear. About 100 ancient root samples of Panax notoginseng , preserved as tribute in the Palace Museum (A.D. 1636 to 1912, Qing dynasty), provided an opportunity to investigate the root size changes during the last 100 years of cultivation. The dry weight of ancient root samples (~120 tou samples, tou represents number of roots per 500 g dry weight) is 0.22-fold of the modern samples with the biggest size (20 tou samples). Transcriptome analysis revealed that PnGAP and PnEXPA4 were highly expressed in 20 tou samples, compared with the 120 tou samples, which might contribute to the thicker cell wall and a higher content of lignin, cellulose, and callose in 20 tou samples. A relatively lower content of dencichine and higher content of ginsenoside Rb1 in 20 tou samples are also consistent with higher expression of ginsenoside biosynthesis-related genes. PnPHL8 was filtrated through transcriptome analysis, which could specifically bind the promoters of PnGAP, PnCYP716A47 , and PnGGPPS3 , respectively. The results in this study represent the first physical evidence of root size changes in P. notoginseng in the last 100 years of cultivation and contribute to a comprehensive understanding of how the cultivation environment affected root size, chemical composition, and clinical application. [ABSTRACT FROM AUTHOR]

Salt stress is a constraint on crop growth and productivity. When exposed to high salt stress, metabolic abnormalities that disrupt reactive oxygen species (ROS) homeostasis result in massive oxygen radical deposition. Dendrobium huoshanense is a perennial orchid herb that thrives in semi-shade conditions. Although lots of studies have been undertaken on abiotic stresses (high temperature, chilling, drought, etc.) of model plants, few studies were reported on the mechanism of salt stress in D. huoshanense. Using a label-free protein quantification method, a total of 2,002 differential expressed proteins were identified in D. huoshanense. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated that proteins involved in vitamin B6 metabolism, photosynthesis, spliceosome, arginine biosynthesis, oxidative phosphorylation, and MAPK signaling were considerably enriched. Remarkably, six malate dehydrogenases (MDHs) were identified from deferentially expressed proteins. (NAD+)-dependent MDH may directly participate in the biosynthesis of malate in the nocturnal crassulacean acid metabolism (CAM) pathway. Additionally, peroxidases such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), as well as antioxidant enzymes involved in glutathione biosynthesis and some vitamins biosynthesis were also identified. Taken together, these results provide a solid foundation for the investigation of the mechanism of salt stress in Dendrobium spp. [ABSTRACT FROM AUTHOR]

Study of the initial steps of the CD95-mediated signaling pathways is a field of intense research and a long list of actors has been described in the literature. Nonetheless, the dynamism of protein-protein interactions (PPIs) occurring in the presence or absence of its natural ligand, CD95L, and the cellular distribution where these PPIs take place render it difficult to predict what will be the cellular outcome associated with the receptor engagement. Accordingly, CD95 stimulation can trigger apoptosis, necroptosis, pyroptosis, or pro-inflammatory signaling pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and phosphatidylinositol-3-kinase (PI3K). Recent data suggest that CD95 can also activate pattern recognition receptors (PRRs) known to sense damage-associated molecular patterns (DAMPs) such as DNA debris and dead cells. This activation might contribute to the pro-inflammatory role of CD95 and favor cancer development or severity of chronic inflammatory and auto-immune disorders. Herein, we discuss some of the molecular links that might connect the CD95 signaling to DAMP sensors. [ABSTRACT FROM AUTHOR]

Mevalonic aciduria (MA) is a severe and rare clinical entity characterized by growth failure, neuropsychomotor development delay, dysmorphic features, periodic fever episodes of involving joints, abdominal organs and skin. Severe gastrointestinal involvement, perianal or gastrointestinal ulcers can be seen rarely.MA is caused by mutations in the gene encoding mevalonate kinase, with the degree of residual enzyme activity largely determining disease severity. Mevalonate kinase is crucial for the biosynthesis of nonsterol isoprenoids, which mediate protein prenylation. These gene defects not only intervene in the mevalonate pathway of cholesterol synthesis but also give rise to episodes of hyperinflammation with increased secretion of interleukin 1b (IL-1β). Although the precise pathogenesis of MA remains unclear, increasing evidence suggests that deficiency in protein prenylation leads to innate immune activation and systemic hyperinflammation. Recent treatment approaches have focused mainly on cytokine-directed biologic therapy because of the understanding of MA as an autoinflammatory disorder. In this paper, we present a 22-year-old female patient with MA disease who had been suffering from recurrent fever attacks, perianal abscesses, and fistulas since her infancy. She has been followed in our clinic since the age of 15 years. She was successfully treated with canakinumab. IL-1 blockade appears to be effective in treating the gastrointestinal complications of MA. [ABSTRACT FROM AUTHOR]

Cotton refers to species in the genus Gossypium that bear spinnable seed coat fibers. A total of 50 species in the genus Gossypium have been described to date. Of these, only four species, viz. Gossypium, hirsutum, G. barbadense, G. arboretum, and G. herbaceum are cultivated; the rest are wild. The black dot-like structures on the surfaces of cotton organs or tissues, such as the leaves, stem, calyx, bracts, and boll surface, are called gossypol glands or pigment glands, which store terpenoid aldehydes, including gossypol. The cotton (Gossypium hirsutum) pigment gland is a distinctive structure that stores gossypol and its derivatives. It provides an ideal system for studying cell differentiation and organogenesis. However, only a few genes involved in the process of gland formation have been identified to date, and the molecular mechanisms underlying gland initiation remain unclear. The terpenoid aldehydes in the lysigenous glands of Gossypium species are important secondary phytoalexins (with gossypol being the most important) and one of the main defenses of plants against pests and diseases. Here, we review recent research on the development of gossypol glands in Gossypium species, the regulation of the terpenoid aldehyde biosynthesis pathway, discoveries from genetic engineering studies, and future research directions. [ABSTRACT FROM AUTHOR]

Ganoderic acid (GA) is an important secondary metabolite of Ganoderma lucidum with a diverse array of pharmacological properties. In this study, we found that exogenous ethylene increased the production of endogenous ethylene and ganoderic acid in G. lucidum. However, the mechanism by which ethylene is regulated remains unclear. As a result, we performed a combined transcriptomics and nontargeted metabolomics analysis to evaluate the regulatory mechanism of ethylene. A total of 4070 differentially expressed genes (1835 up-regulated and 2235 down-regulated) and 378 differentially accumulated metabolites (289 up-regulated and 89 down-regulated) were identified in all groups. The transcriptomics and nontargeted metabolomics data revealed that genes involved in the tricarboxylic acid (TCA) cycle, polyamine metabolic pathway, acetyl-CoA carboxylase (ACC) pathway, and triterpenoid metabolism were up-regulated, whereas the metabolic intermediates involved in these metabolic pathways were down-regulated. These findings imply that ethylene potentially accelerates normal glucose metabolism, hence increasing the number of intermediates available for downstream biological processes, including polyamine metabolism, ethylene synthesis pathway, and ganoderic acid biosynthesis. The findings will contribute significantly to our understanding of secondary metabolites biosynthesis in fungi. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency during the open label extension (weeks 41–113) of the randomized controlled CLUSTER trial. Methods During a 72-week period, patients received open-label canakinumab 150 or 300 mg, every 4 or 8 weeks. The disease activity was evaluated every 8 weeks using physician global assessment and counting the number of flares. Concentrations of CRP and serum amyloid A protein were measured. The safety was studied by determination and classification of observed adverse events. The safety and efficacy were analysed separately in three subgroups of patients receiving a cumulative dose of less than <35 mg/kg, ≥35 to <70 mg/kg or ≥70 mg/kg. Results Of the 74 patients who started the CLUSTER study, 66 entered Epoch 4 and 65 completed it. During the 72-week period, 42 (64%) patients experienced no flares, while 13 (20%) had one flare, as compared with a median of 12 flares per year reported at baseline. Low physician global assessment scores were seen at the end of the study for all groups with >90% reporting minimal disease activity or none at all. Median CRP concentrations were consistently equal or lower than 10 mg/l, while median serum amyloid A concentrations remained only slightly above the normal range of 10 mg/l. The study showed no new or unexpected adverse events. Conclusion Canakinumab proved effective to control disease activity and prevent flares in mevalonate kinase deficiency during the 72-week study period. No new safety concerns were reported. Trial registration NCT02059291. https://clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: Systemic autoinflammatory diseases (SAID) are characterized by inappropriate activation of the innate immune system and include not only monogenic periodic fever syndromes but also multifactorial conditions. As SAID are rare and represent a diagnostic challenge, a multidisciplinary approach is important to ensure successful diagnosis and adequate follow-up of these patients. Objective: To describe the organization of our multidisciplinary SAID clinic and to characterize our clinical experience, highlighting the benefits of multidisciplinary team management. Methods: Our SAID clinic takes place monthly and is managed by pediatric rheumatologists closely collaborating with pediatricians specialized in infectious diseases and immunodeficiencies and one medical geneticist. Patients' data are systematically incorporated in the Rheumatic Diseases Portuguese Register (Reuma.pt). Biological samples are stored in a biobank. We describe our clinical experience based on SAID patients registered into Reuma.pt/SAID between July 2011 and June 2020. Results: We have registered 176 patients, with a median age of disease onset of 3.1 ± 4.4 years and median age at disease diagnosis of 4.7 ± 4.0 years. Most patients were diagnosed with periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome (PFAPA) (n=133), 20 with undefined SAID (uSAID) and 13 with monogenic SAID, including familial Mediterranean fever (FMF) (n=5), tumor necrosis factor receptor-associated periodic syndrome (TRAPS) (n=1), cryopyrin-associated periodic disease (CAPS) (n=1), and hyperimmunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD) (n=2). A genetic test was performed in 31 patients (18%), and in 26% of these a mutation responsible for the phenotype was found. Thirty-four patients (19%) achieved remission. Conclusion: FMF was the most common monogenic SAID and the percentage of patients with an identified causal mutation was low. A structured electronic clinical record coupled with a biobank and a multidisciplinary approach are crucial to ensure successful diagnosis and adequate follow-up of these patients. [ABSTRACT FROM AUTHOR]

Ιnborn errors of immunity (IEI) represents a heterogenous collection of >480 immune system anomalies, leading to severe infections, autoimmune disorders and malignancies. While these conditions are rare globally, their prevalence is notably higher in the Jordanian population, attributed to elevated rates of consanguinity. The intricate nature of IEI has driven the adoption of genomic technologies for the identification of associated genetic defects. In the present study, whole-exome sequencing was performed on nine Jordanian IEI patient samples, confirming germline single-nucleotide variations (SNVs) in 14 genes through Sanger sequencing. Of note, signal transducer and activator of transcription 1 (STAT1), elastase, neutrophil expressed (ELANE) and interferon induced with helicase c domain 1 (IFIH1) harbored mutations that were previously unreported in the Jordanian IEI population. In addition, mutations in capping protein regulator and myosin 1 linker 2 (c.3683C>T), TNFα-induced protein 3-interacting protein 1 (TNIP1) (c.460C>G) and STAT1 (c.1061T>C) were confirmed, marking their association with Jordanian IEI. For robustness, the genomic databases Ensemble, Genome AD and ClinVar were used to confirm the SNVs' associations with IEI. Kyoto Encyclopedia of Genes and Genomes pathway analysis also showed involvement of the IL-17 signaling pathway (including IL-17 receptor A), T-helper type 17 cell differentiation (including STAT1), the JAK-STAT signaling pathway (including STAT2 and tyrosine kinase 2), neutrophil extracellular trap formation (including ELANE), cocaine addiction [G protein signaling modulator 1 (GPSM1)] and cytokine-cytokine receptor interaction (IL-17 receptor C). In summary, exome sequencing identified a likely causative genetic defect in ELANE (PID-28), STAT1 (PID-30) and IFIH1 (PID-33). The present findings reveal the association of novel STAT1, ELANE mutations with the clinical phenotype of the patients, as well as known mutations in NLRP12, GPSM1 and TNIP1, in addition to novel ELANE, STAT1 and IFIH1 mutations associated in the context of Jordanian IEI. [ABSTRACT FROM AUTHOR]

Background: Ginsenoside, as the main active substance in ginseng, has the function of treating various diseases. However, the ginsenosides content of cultivated ginseng is obviously affected by the growth years, but the molecular mechanism is not clear. In addition, there are significant differences in morphology and physiology between wild ginseng and cultivated ginseng, and the effect of growth years on ginsenoside synthesis not yet understood in wild ginseng. Results: Transcriptome sequencing on the roots, stems and leaves of cultivated ginseng and wild ginseng with different growth years was performed in this study, exploring the effect of growth years on gene expression in ginseng. The number of differentially expressed genes (DEGs) from comparison groups in cultivated ginseng was higher than that in wild ginseng. The result of weighted gene co-expression network analysis (WGCNA) showed that growth years significantly affected the gene expression of Mitogen-activated protein kinases (MAPK) signaling pathway and terpenoid backbone biosynthesis pathway in cultivated ginseng, but had no effects in wild ginseng. Furthermore, the growth years had significant effects on the genes related to ginsenoside synthesis in cultivated ginseng, and the effects were different in the roots, stems and leaves. However, it had little influence on the expression of genes related to ginsenoside synthesis in wild ginseng. Growth years might affect the expression of genes for ginsenoside synthesis by influencing the expression of these transcription factors (TFs), like my elob lastosis (MYB), NAM, ATAF1 and 2, and CUC2 (NAC), APETALA2/ethylene-responsive factor (AP2/ERF), basic helix-loop-helix (bHLH) and WRKY, etc., thereby affecting the content of ginsenosides. Conclusions: This study complemented the gaps in the genetic information of wild ginseng in different growth periods and helped to clarify the potential mechanisms of the effect of growth years on the physiological state in wild ginseng and cultivated ginseng, which also provided a new insight into the mechanism of ginsenoside regulation. [ABSTRACT FROM AUTHOR]

Camphor tree [ Cinnamomum camphora (L.) J. Presl], a species in the magnoliid family Lauraceae, is known for its rich volatile oils and is used as a medical cardiotonic and as a scent in many perfumed hygiene products. Here, we present a high-quality chromosome-scale genome of C. camphora with a scaffold N50 of 64.34 Mb and an assembled genome size of 755.41 Mb. Phylogenetic inference revealed that the magnoliids are a sister group to the clade of eudicots and monocots. Comparative genomic analyses identified two rounds of ancient whole-genome duplication (WGD). Tandem duplicated genes exhibited a higher evolutionary rate, a more recent evolutionary history and a more clustered distribution on chromosomes, contributing to the production of secondary metabolites, especially monoterpenes and sesquiterpenes, which are the principal essential oil components. Three-dimensional analyses of the volatile metabolites, gene expression and climate data of samples with the same genotype grown in different locations showed that low temperature and low precipitation during the cold season modulate the expression of genes in the terpenoid biosynthesis pathways, especially TPS genes, which facilitates the accumulation of volatile compounds. Our study lays a theoretical foundation for policy-making regarding the agroforestry applications of camphor tree. [ABSTRACT FROM AUTHOR]

The aerial parts of Agastache rugosa are rich in essential oils containing monoterpenoids, phenylpropanoids, and aromatic compounds. These are used as herbs, perfume plants, and ornamental plants. Based on the difference in the constituents of the essential oil, A. rugosa is divided into pulegone and estragole chemotypes, but the mechanism of key metabolite biosynthesis in these two A. rugosa chemotypes remains unclear. In this study, we compared the morphological differences, metabolite constituents, and transcriptomic data between the two chemotypes of A. rugosa. Monoterpenoid was the main compound in the pulegone chemotype, and phenylpropanoid was the main compound in the estragole chemotype; however, limonene was detected in both chemotypes. Furthermore, 46 genes related to pulegone and estragole biosynthesis were identified. Limonene synthase , limonene-3-hydroxylase , and isopiperitenol dehydrogenase were upregulated in the pulegone chemotype, while phenylalanine ammonia-lyase , 4-coumarate: CoA ligase , CYP73A , coumaroyl-aldehyde dehydrogenase , and eugenol synthase were downregulated in the pulegone chemotype. We identified chavicol methyl transferase and limonene-3-hydroxylase in A. rugosa. This work not only provides the difference in morphology and metabolites in pulegone and estragole chemotypes, but also offers a molecular mechanism of volatile oil biosynthesis, which could be a basis for specialized metabolites in specialized chemotypes. [ABSTRACT FROM AUTHOR]

Ochrophyta is an algal group belonging to the Stramenopiles and comprises diverse lineages of algae which contribute significantly to the oceanic ecosystems as primary producers. However, early evolution of the plastid organelle in Ochrophyta is not fully understood. In this study, we provide a well-supported tree of the Stramenopiles inferred by the large-scale phylogenomic analysis that unveils the eukaryvorous (nonphotosynthetic) protist Actinophrys sol (Actinophryidae) is closely related to Ochrophyta. We used genomic and transcriptomic data generated from A. sol to detect molecular traits of its plastid and we found no evidence of plastid genome and plastid-mediated biosynthesis, consistent with previous ultrastructural studies that did not identify any plastids in Actinophryidae. Moreover, our phylogenetic analyses of particular biosynthetic pathways provide no evidence of a current and past plastid in A. sol. However, we found more than a dozen organellar aminoacyl-tRNA synthases (aaRSs) that are of algal origin. Close relationships between aaRS from A. sol and their ochrophyte homologs document gene transfer of algal genes that happened before the divergence of Actinophryidae and Ochrophyta lineages. We further showed experimentally that organellar aaRSs of A. sol are targeted exclusively to mitochondria, although organellar aaRSs in Ochrophyta are dually targeted to mitochondria and plastids. Together, our findings suggested that the last common ancestor of Actinophryidae and Ochrophyta had not yet completed the establishment of host–plastid partnership as seen in the current Ochrophyta species, but acquired at least certain nuclear-encoded genes for the plastid functions. [ABSTRACT FROM AUTHOR]

Micrarchaeota is a distinctive lineage assigned to the DPANN archaea, which includes poorly characterised microorganisms with reduced genomes that likely depend on interactions with hosts for growth and survival. Here, we report the enrichment of a stable co-culture of a member of the Micrarchaeota (Ca. Micrarchaeum harzensis) together with its Thermoplasmatales host (Ca. Scheffleriplasma hospitalis), as well as the isolation of the latter. We show that symbiont-host interactions depend on biofilm formation as evidenced by growth experiments, comparative transcriptomic analyses and electron microscopy. In addition, genomic, metabolomic, extracellular polymeric substances and lipid content analyses indicate that the Micrarchaeon symbiont relies on the acquisition of metabolites from its host. Our study of the cell biology and physiology of a Micrarchaeon and its host adds to our limited knowledge of archaeal symbioses. The Micrarchaeota lineage includes poorly characterized archaea with reduced genomes that likely depend on host interactions for survival. Here, the authors report a stable co-culture of a member of the Micrarchaeota and its host, and use multi-omic and physiological analyses to shed light on this symbiosis. [ABSTRACT FROM AUTHOR]

Panax vietnamensis Ha et Grushv., an important medicinal plant in Vietnam, consists of several valuable ginsenosides. Compared to other Panax species, molecular and in silico studies concerning its transcriptomes and ginsenoside biosynthesis-related genes are still lacking. In this study, the transcriptomes of 1-year-old leaves and roots of P. vietnamensis were sequenced and analyzed using the Illumina system. The expression of the selected ginsenoside biosynthesis-related genes was confirmed using real-time PCR. In total, 42,724, 41,564, and 43,021 unigenes were assembled for leaves, roots, and leaf and root tissues, respectively. More than 60% of the unigenes from both tissues were functionally annotated using at least one database from the Kyoto encyclopedia of genes and genomes, Pfam, gene ontology, the National Center for Biotechnology Information (NCBI) non-redundant protein sequence database, and the evolutionary genealogy of genes. Furthermore, the expression of the predominant transcripts in each cDNA library was analyzed and identified. In addition, 457 unigenes encoding the enzymes involved in ginsenoside biosynthesis were identified. Most genes encoding enzymes related to ginsenoside biosynthesis via both MVA and non-MVA pathways are indicated. Quantitative PCR analysis showed that β-amyrin synthase (β-AS), cytochrome P450 (CYP716A53v2, CYP716A52v2), and UDP-glycosyl transferase (UGT74AE2) were highly expressed, more so in the roots than in the leaves. Our results may answer the question of how genes are expressed and whether ginsenosides are produced and accumulated in the first growing year of P. vietnamensis leaves and roots. This first comprehensive transcriptome data of 1-year-old leaves and roots of P. vietnamensis is useful for further investigation of ginseng development, biosynthesis, major secondary metabolite pathways, and related gene expression in different tissues and developmental stages. Data also provide useful information for improving ginseng biosynthesis using biotechnology tools. [ABSTRACT FROM AUTHOR]

Background: Although targeting of the cholesterol pathway by statins prevents breast cancer development in mouse models, efficacy is not absolute. Therefore, the goal of this study is to investigate if the upregulation in the cholesterol biosynthesis pathway genes associates with response to statin chemoprevention and may potentially be used as response biomarkers.Methods: Expression of cholesterol biosynthesis pathway genes was initially derived from the RNA sequencing of MCF10A cell line- based breast cancer progression model system and subsequently validated by quantitative PCR assay. Response to fluvastatin was assessed in vitro using the MCF10A cell line model system, including a statin resistant cell line that was generated (MCF10.AT1-R), and measured using colony forming assays. In vivo efficacy of statin for chemoprevention was assessed in the SV40C3 TAg mouse model. Mammary tumors were identified by histologic analysis of the mammary glands. Mammary glands without histologic evidence of high-grade lesions (in situ and/or invasive carcinoma) were considered responsive to statin treatment.Results: We found more than 70% of a published multi-gene fluvastatin resistance signature to be significantly upregulated during breast cancer progression and inversely correlated with statin inhibition of cellular growth and proliferation. This inherent statin resistance gene signature was also largely shared with the signature of acquired resistance to fluvastatin in MCF10.AT1-R cell line model of acquired statin resistance. These inherent resistance genes and genes exclusive to acquired statin resistance map to steroid-, and terpenoid backbone- biosynthesis pathway. We found upregulation of ~ 80% of cholesterol biosynthesis pathway genes in the tumor bearing mammary glands of SV40 C3TAg transgenic mouse model of TNBC, suggesting the involvement of cholesterol biosynthesis pathway in resistance to statin chemoprevention in vivo. A panel of 13-genes from the pathway significantly associated with response to statin treatment, as did the expression level of HMGCR alone in a mouse model of breast cancer suggesting their utility to predict the efficacy of statin chemoprevention.Conclusions: High basal level, or restorative upregulation, in the cholesterol biosynthesis pathway genes appear to be strongly associated with resistance to statin chemoprevention for breast cancer and may serve as a biomarker to tailor statin treatment to individuals who are most likely to benefit. [ABSTRACT FROM AUTHOR]

Vitamin K is a fat-soluble vitamin that mainly exists as phylloquinone or menaquinone in nature. Vitamin K plays an important role in blood clotting and bone health in humans. For use as a nutraceutical, vitamin K is produced by natural extraction, chemical synthesis, and microbial fermentation. Natural extraction and chemical synthesis methods for vitamin K production have limitations, such as low yield of products and environmental concerns. Microbial fermentation is a more sustainable process for industrial production of natural vitamin K than two other methods. Recent advanced genetic technology facilitates industrial production of vitamin K by increasing the yield and productivity of microbial host strains. This review covers (i) general information about vitamin K and microbial host, (ii) current titers of vitamin K produced by wild-type microorganisms, and (iii) vitamin K production by engineered microorganisms, including the details of strain engineering strategies. Finally, current limitations and future directions for microbial production of vitamin K are also discussed. [ABSTRACT FROM AUTHOR]

Rose (Rosa chinensis) is one of the most famous ornamental plants worldwide, with a variety of colors and fragrances. Terpene synthases (TPSs) play critical roles in the biosynthesis of terpenes. In this work, we report a comprehensive study on the genome-wide identification and characterization of the TPS family in R. chinensis. We identified 49 TPS genes in the R. chinensis genome, and they were grouped into five subfamilies (TPS-a, TPS-b, TPS-c, TPS-g and TPS-e/f). Phylogenetics, gene structure and conserved motif analyses indicated that the RcTPS genes possessed relatively conserved gene structures and the RcTPS proteins contained relatively conserved motifs. Multiple putative cis-acting elements involved in the stress response were identified in the promoter region of RcTPS genes, suggesting that some could be regulated by stress. The expression profile of RcTPS genes showed that they were predominantly expressed in the petals of open flowers, pistils, leaves and roots. Under osmotic and heat stresses, the expression of most RcTPS genes was upregulated. These data provide a useful foundation for deciphering the functional roles of RcTPS genes during plant growth as well as addressing the link between terpene biosynthesis and abiotic stress responses in roses. [ABSTRACT FROM AUTHOR]

Plantagos are important economical and medicinal plants that possess several bioactive secondary metabolites, such as phenolics, iridoids, triterpenes, and alkaloids. Triterpenoids are the ubiquitous and dynamic secondary metabolites that are deployed by plants for chemical interactions and protection under biotic/abiotic stress. Plantago ovata, a cultivated species, is the source of psyllium, while Plantago major, a wild species, has significant therapeutic potential. Wild species are considered more tolerant to stressful conditions in comparison to their cultivated allies. In view of this, the present study aimed to decipher the terpenoid biosynthetic pathway operative in P. ovata and P. major using a comparative transcriptomics approach. Majority of terpenoid biosynthetic genes were observed as upregulated in P. major including rate limiting genes of MVA (HMGR) and MEP (DXR) pathways and genes (α-AS, BAS, SM, and CYP716) involved in ursolic acid biosynthesis, an important triterpenoid prevalent in Plantago species. The HPLC output further confirmed the higher concentration of ursolic acid in P. major as compared to P. ovata leaf samples, respectively. In addition to terpenoid biosynthesis, KEGG annotation revealed the involvement of differentially expressed unigenes in several metabolic pathways, aminoacyl-tRNA biosynthesis, biosynthesis of antibiotics, and biosynthesis of secondary metabolites. MYB was found as the most abundant transcription factor family in Plantago transcriptome. We have been able to generate valuable information which can help in improving terpenoid production in Plantago. Additionally, the present study has laid a strong foundation for deciphering other important metabolic pathways in Plantago. [ABSTRACT FROM AUTHOR]

Triterpene saponins exhibit various biological and pharmacological activities. However, the knowledge on saponin biosynthesis in tea plants (Camellia sinensis L.) is still limited. In this work, tea flower and seed samples at different developmental stages and leaves were collected and analyzed with UPLC-PDA-MS and RNA sequencing for saponin determination and transcriptome comparison. The saponin content reached around 19% in the freshly mature seeds and 7% in the green flower buds, and decreased with the fruit ripeness and flower blooming. Almost no saponins were detected in leaf samples. PCA and KEGG analysis suggested that the gene expression pattern and secondary metabolism in TF1 and TS2 vs. leaf samples were significantly different. Weighted gene coexpression network analysis (WGCNA) uncovered two modules related to saponin content. The mevalonate (MVA) instead of 2-C-methyl-d-erythritol-4-phospate (MEP) pathway was responsible for saponin accumulation in tea plants, and 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS), diphosphomevalonate decarboxylase (MVD) and isopentenyl diphosphate isomerase (IDI) may be the key enzymes involved in saponin biosynthesis in tea seeds and flowers. Moreover, ten transcription factors (TFs) were predicted to regulate saponin biosynthesis in the tea plant. Taken together, our study provides a global insight into the saponin biosynthesis and accumulation in the tea plant. [ABSTRACT FROM AUTHOR]

Background: Helicteres angustifolia has long been used in Chinese traditional medicine. It has multiple pharmacological benefits, including anti-inflammatory, anti-viral and anti-tumor effects. Its main active chemicals include betulinic acid, oleanolic acid, helicteric acid, helicterilic acid, and other triterpenoid saponins. It is worth noting that some acylated triterpenoids, such as helicteric acid and helicterilic acid, are characteristic components of Helicteres and are relatively rare among other plants. However, reliance on natural plants as the only sources of these is not enough to meet the market requirement. Therefore, the engineering of its metabolic pathway is of high research value for enhancing the production of secondary metabolites. Unfortunately, there are few studies on the biosynthetic pathways of triterpenoids in H. angustifolia, hindering its further investigation. Results: Here, the RNAs of different groups treated by metabolic stimulation were sequenced with an Illumina high-throughput sequencing platform, resulting in 121 gigabases of data. A total of 424,824 unigenes were obtained after the trimming and assembly of the raw data, and 22,430 unigenes were determined to be differentially expressed. In addition, three oxidosqualene cyclases (OSCs) and four Cytochrome P450 (CYP450s) were screened, of which one OSC (HaOSC1) and one CYP450 (HaCYPi3) achieved functional verification, suggesting that they could catalyze the production of lupeol and oleanolic acid, respectively. Conclusion: In general, the transcriptomic data of H. angustifolia was first reported and analyzed to study functional genes. Three OSCs, four CYP450s and three acyltransferases were screened out as candidate genes to perform further functional verification, which demonstrated that HaOSC1 and HaCYPi3 encode for lupeol synthase and β-amyrin oxidase, which produce corresponding products of lupeol and oleanolic acid, respectively. Their successful identification revealed pivotal steps in the biosynthesis of acylated triterpenoids precursors, which laid a foundation for further study on acylated triterpenoids. Overall, these results shed light on the regulation of acylated triterpenoids biosynthesis. [ABSTRACT FROM AUTHOR]

Covering: 2015 up to July 2021 The market for cosmetics is consumer driven and the desire for green, sustainable and natural ingredients is increasing. The use of isolated enzymes and whole-cell organisms to synthesise these products is congruent with these values, especially when combined with the use of renewable, recyclable or waste feedstocks. The literature of biocatalysis for the synthesis of ingredients in cosmetics in the past five years is herein reviewed. [ABSTRACT FROM AUTHOR]

Dendrobium officinale Kimura et Migo is an important epiphytic plant, belonging to the Orchidaceae family. There are various bioactive components in D. officinal e plants, mainly including polysaccharides, alkaloids, and phenolic compounds. These compounds have been demonstrated to possess multiple functions, such as anti-oxidation, immune regulation, and anti-cancer. Due to serious shortages of wild resources, deterioration of cultivated germplasm and the unstable quality of D. officinale , the study has been focused on the biosynthetic pathway and regulation mechanisms of bioactive compounds. In recent years, with rapid developments in detection technologies and analysis tools, omics research including genomics, transcriptomics, proteomics and metabolomics have all been widely applied in various medicinal plants, including D. officinale. Many important advances have been achieved in D. officinale research, such as chromosome-level reference genome assembly and the identification of key genes involved in the biosynthesis of active components. In this review, we summarize the latest research advances in D. officinal e based on multiple omics studies. At the same time, we discuss limitations of the current research. Finally, we put forward prospective topics in need of further study on D. officinale. [ABSTRACT FROM AUTHOR]

Sindora glabra is an economically important tree that produces abundant oleoresin in the trunk. Here, we present a high-quality chromosome-scale assembly of S. glabra genome by combining Illumina HiSeq, Pacific Biosciences sequencing, and Hi-C technologies. The size of S. glabra genome was 1.11 Gb, with a contig N50 of 1.27 Mb and 31,944 predicted genes. This is the first sequenced genome of the subfamily Caesalpinioideae. As a sister taxon to Papilionoideae, S. glabra underwent an ancient genome triplication shared by core eudicots and further whole-genome duplication shared by early-legume in the last 73.3 million years. S. glabra harbors specific genes and expanded genes largely involved in stress responses and biosynthesis of secondary metabolites. Moreover, 59 terpene backbone biosynthesis genes and 64 terpene synthase genes were identified, which together with co-expressed transcription factors could contribute to the diversity and specificity of terpene compounds and high terpene content in S. glabra stem. In addition, 63 disease resistance NBS-LRR genes were found to be unique in S. glabra genome and their expression levels were correlated with the accumulation of terpene profiles, suggesting potential defense function of terpenes in S. glabra. These together provide new resources for understanding genome evolution and oleoresin production. [ABSTRACT FROM AUTHOR]

Inflammasomes are large intracellular multiprotein complexes, which constitute a novel part of the innate immune system. In response to danger signals from pathogens or other harmful agents, inflammasomes assemble resulting in production of the inflammatory cytokines. We discuss recent knowledge of the role of deregulated inflammasome activity in skin pathologies such as autoinflammatory diseases as well as common skin diseases such as psoriasis and atopic dermatitis. We also present an insight into the activation and effector mechanisms of inflammasomes in skin carcinogenesis. The complex influence of inflammasome on cutaneous disorders raises new challenges and opportunities for the treatment of skin diseases. [ABSTRACT FROM AUTHOR]

Mevalonic aciduria (MA) is the most severe clinical subtype of mevalonate kinase deficiency (MKD) caused by an inherited defect in the mevalonate pathway. The treatment of MKD focuses on the suppression of recurrent hyperinflammatory attacks using anti-inflammatory drugs. Recently, allogeneic hematopoietic stem cell transplantation (HCT) was shown to successfully ameliorate autoinflammatory attacks in patients with MKD. Here, we report a case of an infant who showed severe recurrent systemic inflammation and was diagnosed with MA. Although she responded to steroids, her symptoms relapsed after the dose was tapered, and organ deterioration occurred. Therefore, at the age of 11 months, HCT from a matched, unrelated donor was performed for curative treatment. However, at 50 days after transplantation, acute myeloid leukemia was diagnosed, which was chemo-refractory. A second HCT from her haploidentical father was performed to treat the acute myeloid leukemia, but the patient died of sepsis on day 4 after transplantation. This is the first report of malignancy following HCT for MA. Our findings suggest that normalizing the mevalonate pathway after HCT in patients with MKD impacts patients differently depending on the clinical spectrum and severity of disease. [ABSTRACT FROM AUTHOR]

Background: Mevalonate kinase deficiency (MKD) is a rare autoinflammatory condition caused by biallelic loss-of-function (LOF) mutations in mevalonate kinase (MVK) gene encoding the enzyme mevalonate kinase. Patients with MKD display a variety of non-specific clinical manifestations, which can lead to diagnostic delay. We report the case of a child presenting with vasculitis that was found by genetic testing to be caused by MKD, and now add this autoinflammatory disease to the ever-expanding list of causes of monogenic vasculitides. Case presentation: A 2-year-old male presented with an acute 7-day history of high-grade fever, abdominal pain, diarrhoea, rectal bleeding and extensive purpuric and necrotic lesions, predominantly affecting the lower limbs. He had been suffering from recurrent episodes of fever from early in infancy, associated with maculopapular/petechial rashes triggered by intercurrent infection, and after vaccines. Extensive infection screen was negative. Skin biopsy revealed small vessel vasculitis. Visceral digital subtraction arteriography was normal. With a diagnosis of severe idiopathic cutaneous vasculitis, he was treated with corticosteroids and mycophenolate mofetil. Despite that his acute phase reactants remained elevated, fever persisted and the vasculitic lesions progressed. Next-generation sequencing revealed compound heterozygous mutation in MVK c.928G > A (p.V310M) and c.1129G > A (p.V377I) while reduced mevalonate enzyme activity was confirmed suggesting a diagnosis of MKD as a cause of the severe vasculitis. Prompt targeted treatment with IL-1 blockade was initiated preventing escalation to more toxic vasculitis therapies and reducing unnecessary exposure to cytotoxic treatment. Conclusions: Our report highlights the broad clinical phenotype of MKD that includes severe cutaneous vasculitis and emphasizes the need to consider early genetic screening for young children presenting with vasculitis to exclude a monogenic vasculitis which may be amenable to targeted treatment. [ABSTRACT FROM AUTHOR]

The prevalence of diabetes mellitus has been increasing for decades worldwide. To develop safe and potent therapeutics, animal models contribute a lot to the studies of the mechanisms underlying its pathogenesis. Dietary induction using is a well-accepted protocol in generating insulin resistance and diabetes models. In the present study, we reported the multi-omics profiling of the liver and sera from both peripheral blood and hepatic portal vein blood from Macaca fascicularis that spontaneously developed Type-2 diabetes mellitus with a chow diet (sDM). The other two groups of the monkeys fed with chow diet and high-fat high-sugar (HFHS) diet, respectively, were included for comparison. Analyses of various omics datasets revealed the alterations of high consistency. Between the sDM and HFHS monkeys, both the similar and unique alterations in the lipid metabolism have been demonstrated from metabolomic, transcriptomic, and proteomic data repeatedly. The comparison of the proteome and transcriptome confirmed the involvement of fatty acid binding protein 4 (FABP4) in the diet-induced pathogenesis of diabetes in macaques. Furthermore, the commonly changed genes between spontaneous diabetes and HFHS diet-induced prediabetes suggested that the alterations in the intra- and extracellular structural proteins and cell migration in the liver might mediate the HFHS diet induction of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Various agricultural products used in food fermentation are polluted by heavy metals, especially copper, which seriously endangers human health. Methods to remove copper with microbial strategies have gained interests. A novel Meyerozyma guilliermondii GXDK6 could survive independently under high stress of copper (1400 ppm). The copper tolerance mechanism of GXDK6 was revealed by integrated omics in this work. Whole-genome analysis showed that nine genes (i.e., CCC2 , CTR3 , FRE2 , GGT , GST , CAT , SOD2 , PXMP4 , and HSP82) were related to GXDK6 copper tolerance. Copper stress elevated glutathione metabolism-related gene expression, glutathione content, and glutathione sulfur transferase activity, suggesting enhanced copper conjugation and detoxification in cells. The inhibited copper uptake by Ctr3 and enhanced copper efflux by Ccc2 contributed to the decrease in intracellular copper concentration. The improved expression of antioxidant enzyme genes (PXMP4 , SOD2 , and CAT), accompanied by the enhanced activities of antioxidant enzymes (peroxidase, superoxide dismutase, and catalase), decreased copper-induced reactive oxygen species production, protein carbonylation, lipid peroxidation, and cell death. The metabolite D-mannose against harsh stress conditions was beneficial to improving copper tolerance. This study contributed to understanding the copper tolerance mechanism of M. guilliermondii and its application in removing copper during fermentation. [ABSTRACT FROM AUTHOR]

Background: Bupleurum chinense DC. is a widely used traditional Chinese medicinal plant. Saikosaponins are the major bioactive constituents of B. chinense, but relatively little is known about saikosaponin biosynthesis. In the present study, we performed an integrated analysis of metabolic composition and the expressed genes involved in saikosaponin biosynthetic pathways among four organs (the root, flower, stem, and leaf) of B. chinense to discover the genes related to the saikosaponin biosynthetic pathway. Results: Transcript and metabolite profiles were generated through high-throughput RNA-sequencing (RNA-seq) data analysis and liquid chromatography tandem mass spectrometry, respectively. Evaluation of saikosaponin contents and transcriptional changes showed 152 strong correlations (P < 0.05) over 3 compounds and 77 unigenes. These unigenes belonged to eight gene families: the acetoacetyl CoA transferase (AACT) (6), HMG-CoA synthase (HMGS) (2), HMG-CoA reductase (HMGR) (2), mevalonate diphosphate decarboxylase (MVD) (1), 1-deoxy-D-xylulose-5-phosphate synthase (DXS) (3), farnesyl diphosphate synthase (FPPS) (11), β-amyrin synthase (β-AS) (13) and cytochrome P450 enzymes (P450s) (39) families. Conclusions: Our results investigated the diversity of the saikosaponin triterpene biosynthetic pathway in the roots, stems, leaves and flowers of B. chinese by integrated transcriptomic and metabolomic analysis, implying that manipulation of P450s genes such as Bc95697 and Bc35434 might improve saikosaponin biosynthesis. This is a good candidate for the genetic improvement of this important medicinal plant. [ABSTRACT FROM AUTHOR]

The root of Panax notoginseng (Burk.), in which saponins are the major active components, is a famous traditional Chinese medicine used to stop bleeding and to decrease inflammation and heart disease. Inflorescence removal increases the yield and quality of P. notoginseng , but the underlying molecular mechanisms are unknown. Here, the differences between inflorescence-removal treatment and control groups of P. notoginseng were compared using transcriptomics and metabolomics analyses. Illumina sequencing of cDNA libraries prepared from the rhizomes, leaves and roots of the two groups independently identified 6,464, 4,584, and 7,220 differentially expressed genes (DEG), respectively. In total, 345 differentially expressed transcription factors (TFs), including MYB and WRKY family members, were induced by the inflorescence-removal treatment. Additionally, 215 DEGs involved in saponin terpenoid backbone biosynthetic pathways were identified. Most genes involved in the mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways were activated by inflorescence removal. The co-expression analysis showed that the low expression levels of flavonoid biosynthesis-related genes (e.g., C4H and F3H) decreased the biosynthesis and accumulation of some flavonoids after inflorescence removal. The results not only provide new insights into the fundamental mechanisms underlying the poorly studied inflorescence-removal process in P. notoginseng and other rhizome crops, but they also represent an important resource for future research on gene functions during inflorescence-removal treatments and the reproductive stage. [ABSTRACT FROM AUTHOR]