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BACKGROUND: Massa Medicata Fermentata (MMF) is one of the most commonly used traditional fermented Chinese medicines. MMF is widely used for the treatment of digestive diseases such as dyspepsia and flatulence in traditional Chinese medicine (TCM). However, the therapeutic mechanism of MMF is not well understood. METHOD: In this study, SD rats received 0.1% iodoacetamide either alone or in combination with water platform sleep deprivation to induce functional dyspepsia and were administered MMF (1 or 3 g/kg/d, ig), mosapride citrate (Mosa., 2 mg/kg/d, ig) or saline for 21 days. After treatment, the sucrose preferences and gastric emptying rates of the rats were assessed; HE staining was used to detect the pathological changes in the rat duodenum; ELISA kits were used to detect motilin (MTL) in the rat duodenum and the serum contents of Interferon-λ (IFN-λ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-α (TNF-α). An approach based on 16S rDNA amplicon sequencing was utilized to explore the intestinal microflora in the colon contents of rats and the metabolism of the microflora to assess the potential mechanisms of MMF in ameliorating functional dyspepsia (FD). In addition, gas chromatography-mass spectrometry (GC/MS) was used to detect changes in short fatty acids (SCFAs) in the colon contents of rats. RESULTS: MMF reduced the serum levels of TNF-α, and IFN-λ, improved the morphology of duodenal intestinal villi and ameliorated intestinal mucosal lamina propria injury in FD rats, and the sucrose preference increased and the gastric emptying rate decreased in FD rats. MMF alleviated intestinal microflora disturbance and exerted a regulatory effect on Bacteroidetes, Proteobacteria, and Firmicutes, reduced total SCAFs, Butyric Acid, Propionic acid-2-methyl, Butanoic Acid-3-methyl, and Hexanoic acid. CONCLUSIONS: These results showed that the effect of MMF on the intestinal flora and its metabolites may provide a new treatment strategy for FD.
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Dispepsia , Microbioma Gastrointestinal , Ratos , Animais , Dispepsia/tratamento farmacológico , Dispepsia/microbiologia , Microbioma Gastrointestinal/genética , Fator de Necrose Tumoral alfa/metabolismo , Ratos Sprague-DawleyRESUMO
INTRODUCTION: The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are hexanucleotide repeats in chromosome 9 open reading frame 72 (C9orf72). These repeats produce dipeptide repeat proteins with poly(PR) being the most toxic one. METHODS: We performed a kinome-wide CRISPR/Cas9 knock-out screen in human induced pluripotent stem cell (iPSC) -derived cortical neurons to identify modifiers of poly(PR) toxicity, and validated the role of candidate modifiers using in vitro, in vivo, and ex-vivo studies. RESULTS: Knock-down of NIMA-related kinase 6 (NEK6) prevented neuronal toxicity caused by poly(PR). Knock-down of nek6 also ameliorated the poly(PR)-induced axonopathy in zebrafish and NEK6 was aberrantly expressed in C9orf72 patients. Suppression of NEK6 expression and NEK6 activity inhibition rescued axonal transport defects in cortical neurons from C9orf72 patient iPSCs, at least partially by reversing p53-related DNA damage. DISCUSSION: We identified NEK6, which regulates poly(PR)-mediated p53-related DNA damage, as a novel therapeutic target for C9orf72 FTD/ALS.
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Esclerose Lateral Amiotrófica , Demência Frontotemporal , Células-Tronco Pluripotentes Induzidas , Animais , Humanos , Esclerose Lateral Amiotrófica/genética , Demência Frontotemporal/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Proteína C9orf72/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Sistemas CRISPR-Cas , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Neurônios/metabolismo , Expansão das Repetições de DNA/genética , Quinases Relacionadas a NIMA/genética , Quinases Relacionadas a NIMA/metabolismoRESUMO
Clausena lansium (Lour.) Skeels (Rutaceae), recognized as wampee, is a widely distributed fruit tree which is utilized as a folk-medicine for treatment of several common diseases. However, the genomic information about this medicinally important species is still lacking. Therefore, we assembled the first genome of Clausena genus with a total length of 310.51 Mb and scaffold N50 of 2.24 Mb by using 10× Genomics technology. Further annotation revealed a total of 34,419 protein-coding genes, while repetitive elements covered 39.08% (121.36 Mb) of the genome. The Clausena and Citrus genus were found to diverge around 22 MYA, and also shared an ancient whole-genome triplication event with Vitis. Furthermore, multi-tissue transcriptomic analysis enabled the identification of genes involved in the synthesis of carbazole alkaloids. Altogether, these findings provided new insights into the genome evolution of Wampee species and highlighted the possible role of key genes involved in the carbazole alkaloids biosynthetic pathway.
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Alcaloides , Clausena , Carbazóis , Clausena/genética , Frutas , Estrutura MolecularRESUMO
m6A (N6-methyladenosine) methylation, a well-known modification in tumour epigenetics, dynamically and reversibly fine tunes the entire process of RNA metabolism. Aberrant levels of m6A and its regulators, which can predict the survival and outcomes of cancer patients, are involved in tumorigenesis, metastasis and resistance. Ovarian cancer (OC) ranks first among gynaecological tumours in the causes of death. At first diagnosis, patients with OC are usually at advanced stages owing to a lack of early biomarkers and effective targets. After treatment, patients with OC often develop drug resistance. This article reviews the recent experimental advances in understanding the role of m6A modification in OC, raising the possibility to treat m6A modification and its regulators as promising diagnostic markers and therapeutic targets for OC.
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Perilla frutescens (L.) Britton is a classic herbal plant used widely against asthma in China. But its mechanism of beneficial effect remains undermined. In the study, the antiallergic asthma effects of Perilla leaf extract (PLE) were investigated, and the underlying mechanism was also explored. Results showed that PLE treatment significantly attenuated airway inflammation in OVA-induced asthma mice, by ameliorating lung pathological changes, inhibiting recruitment of inflammatory cells in lung tissues and bronchoalveolar lavage fluid (BALF), decreasing the production of inflammatory cytokines in the BALF, and reducing the level of immunoglobulin in serum. PLE treatment suppressed inflammatory response in antigen-induced rat basophilic leukemia 2H3 (RBL-2H3) cells as well as in OVA-induced human peripheral blood mononuclear cells (PBMCs). Furthermore, PLE markedly inhibited the expression and phosphorylation of Syk, NF-κB, PKC, and cPLA2 both in vivo and in vitro. By cotreating with inhibitors (BAY61-3606, Rottlerin, BAY11-7082, and arachidonyl trifluoromethyl ketone) in vitro, results revealed that PLE's antiallergic inflammatory effects were associated with the inhibition of Syk and its downstream signals NF-κB, PKC, and cPLA2. Collectively, the present results suggested that PLE could attenuate allergic inflammation, and its mechanism might be partly mediated through inhibiting the Syk pathway.
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Asma , Perilla , Animais , Asma/metabolismo , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Pulmão/metabolismo , Camundongos , NF-kappa B/metabolismo , Perilla/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Transdução de SinaisRESUMO
The low-grade, chronic inflammation initiated by TLR4-triggered innate immune responses has a central role on early osteoarthritis. Amurensin H is a resveratrol dimer with anti-inflammatory and anti-apoptotic effects, while its effects on TLR-4 signals to inhibit osteoarthritis are still unclear. In the present study, treatment with amurensin H for 2 weeks in monosodium iodoacetate-induced mice significantly slows down cartilage degeneration and inflammation using macroscopic evaluation, haematoxylin and eosin (HE) staining and micro-magnetic resonance imaging. In IL-1ß-stimulated rat chondrocytes, amurensin H suppresses the production of inflammatory mediators including nitric oxide, IL-6, IL-17, PGE2 and TNF-α using Greiss and ELISA assay. Amurensin H inhibits matrix degradation via decreasing levels of MMP-9 and MMP-13 using Western blot assay, promotes synthesis of type II collagen and glycosaminoglycan using immunostaining and safranin O staining, respectively. Amurensin H inhibits intracellular and mitochondrial reactive oxygen species (ROS) generation, and mitochondrial membrane depolarization using DCFH-DA, MitoSOX Red and JC-1 assay as well. IL-1ß stimulates TLR4 activation and Syk phosphorylation in chondrocytes, while amurensin H inhibits TLR4/Syk signals and downstream p65 phosphorylation and translocation in a time and dose-dependent manner. Together, these results suggest that amurensin H exerts chondroprotective effects by attenuating oxidative stress, inflammation and matrix degradation via the TLR4/Syk/NF-κB pathway.
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Anti-Inflamatórios/farmacologia , Benzofuranos/farmacologia , Condrócitos/metabolismo , Condrócitos/patologia , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Estilbenos/farmacologia , Quinase Syk/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Benzofuranos/química , Condrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Iodoacetatos , Camundongos , Modelos Biológicos , Osteoartrite/induzido quimicamente , Osteoartrite/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estilbenos/química , Fator de Transcrição RelA/metabolismoRESUMO
BACKGROUND & AIMS: The variety of alterations found in hepatocellular carcinoma (HCC) makes the identification of functionally relevant genes and their combinatorial actions in tumorigenesis challenging. Deregulation of receptor tyrosine kinases (RTKs) is frequent in HCC, yet little is known about the molecular events that cooperate with RTKs and whether these cooperative events play an active role at the root of liver tumorigenesis. METHODS: A forward genetic screen was performed using Sleeping Beauty transposon insertional mutagenesis to accelerate liver tumour formation in a genetic context in which subtly increased MET RTK levels predispose mice to tumorigenesis. Systematic sequencing of tumours identified common transposon insertion sites, thus uncovering putative RTK cooperators for liver cancer. Bioinformatic analyses were applied to transposon outcomes and human HCC datasets. In vitro and in vivo (through xenografts) functional screens were performed to assess the relevance of distinct cooperative modes to the tumorigenic properties conferred by RTKs. RESULTS: We identified 275 genes, most of which are altered in patients with HCC. Unexpectedly, these genes are not restricted to a small set of pathway/cellular processes, but cover a large spectrum of cellular functions, including signalling, metabolism, chromatin remodelling, mRNA degradation, proteasome, ubiquitination, cell cycle regulation, and chromatid segregation. We validated 15 tumour suppressor candidates, as shRNA-mediated targeting confers tumorigenicity to RTK-sensitized cells, but not to cells with basal RTK levels. This demonstrates that the context of enhanced RTK levels is essential for their action in tumour initiation. CONCLUSION: Our study identifies unanticipated genetic interactions underlying gene cooperativity with RTKs in HCC. Moreover, these results show how subtly increased levels of wild-type RTKs provide a tumour permissive cellular environment allowing a large spectrum of deregulated mechanisms to initiate liver cancer. LAY SUMMARY: Receptor tyrosine kinases (RTKs) are among signals frequently deregulated in patients with hepatocellular carcinoma and their deregulation confers essential biological properties to cancer cells. We have applied a genetic method to randomly mutate large numbers of genes in the context of a mouse model with increased RTK levels, predisposed to develop liver cancer. We identified mechanisms that accelerate tumour formation in cooperation with enhanced RTK levels. The wide array of cellular functions among these cooperators illustrates an extraordinary capability of RTKs to render the liver more vulnerable to additional alterations, by priming cells for tumour initiation.
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Carcinogênese/genética , Carcinoma Hepatocelular , Neoplasias Hepáticas , Fígado/patologia , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/genética , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Mutagênese Insercional , Receptores Proteína Tirosina Quinases/genética , Transdução de SinaisRESUMO
Genetic mutations leading to oncogenic variants of receptor tyrosine kinases (RTKs) are frequent events during tumorigenesis; however, the cellular vulnerability to nononcogenic RTK fluctuations has not been characterized. Here, we demonstrated genetically that in the liver subtle increases in wild-type Met RTK levels are sufficient for spontaneous tumors in mice (Alb-R26Met ), conceptually illustrating how the shift from physiological to pathological conditions results from slight perturbations in signaling dosage. By analyzing 96 different genes in a panel of tumor samples, we demonstrated that liver tumorigenesis modeled by Alb-R26Met mice corresponds to a subset of hepatocellular carcinoma (HCC) patients, thus establishing the clinical relevance of this HCC mouse model. We elucidated the regulatory networks underlying tumorigenesis by combining a phosphokinome screen with bioinformatics analysis. We then used the signaling diversity results obtained from Alb-R26Met HCC versus control livers to design an "educated guess" drug screen, which led to the identification of new, deleterious synthetic lethal interactions. In particular, we report synergistic effects of mitogen-activated protein kinase kinase, ribosomal S6 kinase, and cyclin-dependent kinase 1/2 in combination with Bcl-XL inhibition on a panel of liver cancer cells. Focusing on mitogen-activated protein kinase kinase and Bcl-XL targeting, we mechanistically demonstrated concomitant down-regulation of phosphorylated extracellular signal-regulated kinase and myeloid cell leukemia 1 levels. Of note, a phosphorylated extracellular signal-regulated kinase+/BCL-XL+ /myeloid cell leukemia 1+ signature, deregulated in Alb-R26Met tumors, characterizes a subgroup of HCC patients with poor prognosis. CONCLUSION: Our genetic studies highlight the heightened vulnerability of liver cells to subtle changes in nononcogenic RTK levels, allowing them to acquire a molecular profile that facilitates the full tumorigenic program; furthermore, our outcomes uncover new synthetic lethal interactions as potential therapies for a cluster of HCC patients. (Hepatology 2017;66:1644-1661).
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Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas Experimentais/enzimologia , Receptores Proteína Tirosina Quinases/metabolismo , Animais , Carcinogênese , Carcinoma Hepatocelular/genética , Linhagem Celular , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fígado/enzimologia , Neoplasias Hepáticas Experimentais/genética , Camundongos Transgênicos , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Terapia de Alvo Molecular , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Receptores Proteína Tirosina Quinases/genética , Proteína bcl-X/antagonistas & inibidores , Proteína bcl-X/metabolismoRESUMO
MicroRNAs (miRNAs) can regulate nearly all biological processes and their dysregulation is implicated in various complex diseases and pathological conditions. Recent years have seen a growing number of functional studies of miRNAs using high-throughput experimental technologies, which have produced a large amount of high-quality data regarding miRNA target genes and their interactions with small molecules, long non-coding RNAs, epigenetic modifiers, disease associations, etc These rich sets of information have enabled the creation of comprehensive networks linking miRNAs with various biologically important entities to shed light on their collective functions and regulatory mechanisms. Here, we introduce miRNet, an easy-to-use web-based tool that offers statistical, visual and network-based approaches to help researchers understand miRNAs functions and regulatory mechanisms. The key features of miRNet include: (i) a comprehensive knowledge base integrating high-quality miRNA-target interaction data from 11 databases; (ii) support for differential expression analysis of data from microarray, RNA-seq and quantitative PCR; (iii) implementation of a flexible interface for data filtering, refinement and customization during network creation; (iv) a powerful fully featured network visualization system coupled with enrichment analysis. miRNet offers a comprehensive tool suite to enable statistical analysis and functional interpretation of various data generated from current miRNA studies. miRNet is freely available at http://www.mirnet.ca.
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Redes Reguladoras de Genes , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Software , Animais , Sítios de Ligação , Gráficos por Computador , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Internet , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Transdução de SinaisRESUMO
The successive events that cells experience throughout development shape their intrinsic capacity to respond and integrate RTK inputs. Cellular responses to RTKs rely on different mechanisms of regulation that establish proper levels of RTK activation, define duration of RTK action, and exert quantitative/qualitative signalling outcomes. The extent to which cells are competent to deal with fluctuations in RTK signalling is incompletely understood. Here, we employ a genetic system to enhance RTK signalling in a tissue-specific manner. The chosen RTK is the hepatocyte growth factor (HGF) receptor Met, an appropriate model due to its pleiotropic requirement in distinct developmental events. Ubiquitously enhanced Met in Cre/loxP-based Rosa26(stopMet) knock-in context (Del-R26(Met)) reveals that most tissues are capable of buffering enhanced Met-RTK signalling thus avoiding perturbation of developmental programs. Nevertheless, this ubiquitous increase of Met does compromise selected programs such as myoblast migration. Using cell-type specific Cre drivers, we genetically showed that altered myoblast migration results from ectopic Met expression in limb mesenchyme rather than in migrating myoblasts themselves. qRT-PCR analyses show that ectopic Met in limbs causes molecular changes such as downregulation in the expression levels of Notum and Syndecan4, two known regulators of morphogen gradients. Molecular and functional studies revealed that ectopic Met expression in limb mesenchyme does not alter HGF expression patterns and levels, but impairs HGF bioavailability. Together, our findings show that myoblasts, in which Met is endogenously expressed, are capable of buffering increased RTK levels, and identify mesenchymal cells as a cell type vulnerable to ectopic Met-RTK signalling. These results illustrate that embryonic cells are sensitive to alterations in the spatial distribution of RTK action, yet resilient to fluctuations in signalling levels of an RTK when occurring in its endogenous domain of activity.
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Desenvolvimento Embrionário/genética , Fator de Crescimento de Hepatócito/genética , Mioblastos/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Animais , Movimento Celular/genética , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento , Fator de Crescimento de Hepatócito/metabolismo , Camundongos , Fosforilação , Proteínas Proto-Oncogênicas c-met/biossíntese , Transdução de Sinais , Sindecana-4/biossíntese , Sindecana-4/genéticaRESUMO
The Hong Kong Jellyfish Project is a citizen science initiative started in early 2021 to enhance our understanding of jellyfish in Hong Kong. Here, we present a dataset of jellyfish sightings collected by citizen scientists from 2021 through 2023 within local waters. Citizen scientists submitted photographs and other data (time, date, and location) using a website, iNaturalist project, and social media. Sightings were validated using references from the literature. A total of 1,020 usable observations are included in this dataset, showing the occurrence and distribution of jellyfish in Hong Kong in 2021-2023. This dataset is now publicly available and discoverable in the Global Biodiversity Information Facility database and is available for download. This data can be used to enhance our understanding of the biodiversity of local marine ecosystems.
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Parasitic plants have evolved to be subtly or severely dependent on host plants to complete their life cycle. To provide new insights into the biology of parasitic plants in general, we assembled genomes for members of the sandalwood order Santalales, including a stem hemiparasite (Scurrula) and two highly modified root holoparasites (Balanophora) that possess chimaeric host-parasite tubers. Comprehensive genome comparisons reveal that hemiparasitic Scurrula has experienced a relatively minor degree of gene loss compared with autotrophic plants, consistent with its moderate degree of parasitism. Nonetheless, patterns of gene loss appear to be substantially divergent across distantly related lineages of hemiparasites. In contrast, Balanophora has experienced substantial gene loss for the same sets of genes as an independently evolved holoparasite lineage, the endoparasitic Sapria (Malpighiales), and the two holoparasite lineages experienced convergent contraction of large gene families through loss of paralogues. This unprecedented convergence supports the idea that despite their extreme and strikingly divergent life histories and morphology, the evolution of these and other holoparasitic lineages can be shaped by highly predictable modes of genome reduction. We observe substantial evidence of relaxed selection in retained genes for both hemi- and holoparasitic species. Transcriptome data also document unusual and novel interactions between Balanophora and host plants at the host-parasite tuber interface tissues, with evidence of mRNA exchange, substantial and active hormone exchange and immune responses in parasite and host.
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Interações Hospedeiro-Parasita , Plantas , Interações Hospedeiro-Parasita/genética , Plantas/genéticaRESUMO
Despite improved methods of diagnosis and the development of different treatments, mortality from lung cancer remains surprisingly high. Non-small cell lung cancer (NSCLC) accounts for the large majority of lung cancer cases. Therefore, it is important to review current methods of diagnosis and treatments of NSCLC in the clinic and preclinic. In this review, we describe, as a guide for clinicians, current diagnostic methods and therapies (such as chemotherapy, chemoradiotherapy, targeted therapy, antiangiogenic therapy, immunotherapy, and combination therapy) for NSCLC.
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Citrus grandis 'Tomentosa' (CGT) (Huajuhong, HJH) is a widely used medicinal plant, which is mainly produced in Guangdong and Guangxi provinces of South China. Particularly, HJH from Huazhou (HZ) county of Guangdong province has been well-regarded as the best national product for geo-herbalism. But the reasons for geo-herbalism property in HJH from HZ county remains a mystery. Therefore, a multi-omics approach was applied to identify the nature of the geo-herbalism in CGT from three different regions. The comprehensive screening of differential metabolites revealed that the Nobiletin content was significantly different in HZ region compared to other regions, and could be employed as a key indicator to determine the geo-herbalism. Furthermore, the high-quality genome (N50 of 9.12 Mb), coupled with genomics and transcriptomics analyses indicated that CGT and Citrus grandis are closely related, with a predicted divergence time of 19.1 million years ago (MYA), and no recent WGD occurred in the CGT, and the bioactive ingredients of CGT were more abundant than that of Citrus grandis. Interestingly, Nobiletin (Polymethoxyflavones) content was identified as a potential indicator of geo-herbalism, and O-methyltransferase (OMT) genes are involved in the synthesis of Polymethoxyflavones. Further multi-omics analysis led to the identification of a novel OMT gene (CtgOMT1) whose transient overexpression displayed significantly higher Nobiletin content, suggesting that CtgOMT1 was involved in the synthesis of Nobiletin. Overall, our findings provide new data resources for geo-herbalism evaluation, germplasm conservation and insights into Nobiletin biosynthesis pathways for the medicinal plant C. grandis 'Tomentosa'.
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Citrus , Plantas Medicinais , Citrus/genética , Medicina Herbária , China , Plantas Medicinais/genéticaRESUMO
Cycads represent one of the most ancient lineages of living seed plants. Identifying genomic features uniquely shared by cycads and other extant seed plants, but not non-seed-producing plants, may shed light on the origin of key innovations, as well as the early diversification of seed plants. Here, we report the 10.5-Gb reference genome of Cycas panzhihuaensis, complemented by the transcriptomes of 339 cycad species. Nuclear and plastid phylogenomic analyses strongly suggest that cycads and Ginkgo form a clade sister to all other living gymnosperms, in contrast to mitochondrial data, which place cycads alone in this position. We found evidence for an ancient whole-genome duplication in the common ancestor of extant gymnosperms. The Cycas genome contains four homologues of the fitD gene family that were likely acquired via horizontal gene transfer from fungi, and these genes confer herbivore resistance in cycads. The male-specific region of the Y chromosome of C. panzhihuaensis contains a MADS-box transcription factor expressed exclusively in male cones that is similar to a system reported in Ginkgo, suggesting that a sex determination mechanism controlled by MADS-box genes may have originated in the common ancestor of cycads and Ginkgo. The C. panzhihuaensis genome provides an important new resource of broad utility for biologists.
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Cycas , Cycadopsida/genética , Cycas/genética , Genes de Plantas , Ginkgo biloba/genética , Filogenia , Sementes/genéticaRESUMO
Rosa rugosa, commonly known as rugged rose, is a perennial ornamental shrub. It produces beautiful flowers with a mild fragrance and colorful seed pods. Unlike many other cultivated roses, R. rugosa adapts to a wide range of habitat types and harsh environmental conditions such as salinity, alkaline, shade, drought, high humidity, and frigid temperatures. Here, we produced and analyzed a high-quality genome sequence for R. rugosa to understand its ecology, floral characteristics and evolution. PacBio HiFi reads were initially used to construct the draft genome of R. rugosa, and then Hi-C sequencing was applied to assemble the contigs into 7 chromosomes. We obtained a 382.6 Mb genome encoding 39,704 protein-coding genes. The genome of R. rugosa appears to be conserved with no additional whole-genome duplication after the gamma whole-genome triplication (WGT), which occurred ~100 million years ago in the ancestor of core eudicots. Based on a comparative analysis of the high-quality genome assembly of R. rugosa and other high-quality Rosaceae genomes, we found a unique large inverted segment in the Chinese rose R. chinensis and a retroposition in strawberry caused by post-WGT events. We also found that floral development- and stress response signaling-related gene modules were retained after the WGT. Two MADS-box genes involved in floral development and the stress-related transcription factors DREB2A-INTERACTING PROTEIN 2 (DRIP2) and PEPTIDE TRANSPORTER 3 (PTR3) were found to be positively selected in evolution, which may have contributed to the unique ability of this plant to adapt to harsh environments. In summary, the high-quality genome sequence of R. rugosa provides a map for genetic studies and molecular breeding of this plant and enables comparative genomic studies of Rosa in the near future.
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BACKGROUND: Perilla frutescens (L.) Britt., a classic medicinal plant, has been demonstrated to have anti-inflammatory and anti-allergic effects in asthma. Perilla leaves extract (PLE) exerted significant therapeutic effect against allergic asthma inflammation through Syk inhibition. But the active chemical ingredients from PLE are complex and unclear, it is difficult to fully elucidate its pharmacological mechanisms. METHODS: A method was established for rapid screening and characterization of active ingredients from PLE that targeted Syk, with which three potential active ingredients were identified. By using OVA-induced allergic asthma mouse model in vivo, OVA-induced human PBMCs inflammation model and DNP-IgE/BSA-induced RBL-2H3 cells model in vitro, the effects and mechanisms of PLE and its active components were evaluated. RESULTS: Using Syk-affinity screening method, roseoside (RosS), vicenin-2 (Vic-2) and rosmarinic acid (RosA) were identified from PLE. In vitro, PLE and its ingredients showed significant inhibitory activities against Syk, with their mixture (Mix, prepared by RosS, Vic-2 and RosA in accordance with their ratio in Syk-conjugated beads bound fraction) showing a stronger inhibitory activity. RosS, Vic-2 and RosA also showed significant effects on allergic asthma, and a synergistic effect of Mix was observed. Moreover, treatment with PLE, RosS, Vic-2, RosA, and Mix significantly inhibited the expression and phosphorylation of Syk, PKC, NF-κB p65, and cPLA2 in allergic mice lung tissue and in RBL-2H3 cells. CONCLUSION: PLE may alleviate allergic airway inflammation partly through the multiple components synergistic targeting on Syk and its downstream inflammatory pathway.
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Nyssa yunnanensis is a deciduous tree species in the family Nyssaceae within the order Cornales. As only eight individual trees and two populations have been recorded in China's Yunnan province, this species has been listed among China's national Class I protection species since 1999 and also among 120 PSESP (Plant Species with Extremely Small Populations) in the Implementation Plan of Rescuing and Conserving China's Plant Species with Extremely Small Populations (PSESP) (2011-2-15). Here, we present the draft genome assembly of N. yunnanensis. Using 10X Genomics linked-reads sequencing data, we carried out the de novo assembly and annotation analysis. The N. yunnanensis genome assembly is 1475 Mb in length, containing 288,519 scaffolds with a scaffold N50 length of 985.59 kb. Within the assembled genome, 799.51 Mb was identified as repetitive elements, accounting for 54.24% of the sequenced genome, and a total of 39,803 protein-coding genes were predicted. With the genomic characteristics of N. yunnanensis available, our study might facilitate future conservation biology studies to help protect this extremely threatened tree species.
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Osteonecrosis of the femoral head is a common orthopedic disease. Based on years of clinical experience and significant imaging data, this study aimed to elucidate a new type of it, to help improve prognosis in young adults and provide a basis for hip preservation treatment.From January 2014 to December 2016, a total of 211 patients undergoing hip preservation surgery for femoral head necrosis at our hospital were enrolled in this study. Coronal plane classification and cross-sectional area analysis were performed by nuclear magnetic resonance imaging (computed tomography optional) in cases meeting the inclusion criteria. Meanwhile, a new method of classification and calculating the necrotic area was proposed. The application simulation was conducted using sample cases. Additionally, treatment methods were recommended. We used our method to compare the outcome of the selected patients with the JIC classification so as to judge the advantages and disadvantages.The " pressure bone trabecular angle " of the femoral head was measured, and the "sclerotic band" (Zhang Ying) type of classification system and the "quartile" (Zhang Ying) method of measurement were used in 2 sample cases. After analysis, it is more accurate than JIC.The "Sclerotic band" type of classification system and 'quartile' methods are new methods to evaluate the stability of femoral head necrosis. They are convenient for clinical application and easily adopted.
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Necrose da Cabeça do Fêmur/classificação , Necrose da Cabeça do Fêmur/patologia , Adulto , Osso Esponjoso/patologia , Feminino , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Averrhoa carambola is commonly known as star fruit because of its peculiar shape, and its fruit is a rich source of minerals and vitamins. It is also used in traditional medicines in countries such as India, China, the Philippines, and Brazil for treating various ailments, including fever, diarrhea, vomiting, and skin disease. Here, we present the first draft genome of the Oxalidaceae family, with an assembled genome size of 470.51 Mb. In total, 24,726 protein-coding genes were identified, and 16,490 genes were annotated using various well-known databases. The phylogenomic analysis confirmed the evolutionary position of the Oxalidaceae family. Based on the gene functional annotations, we also identified enzymes that may be involved in important nutritional pathways in the star fruit genome. Overall, the data from this first sequenced genome in the Oxalidaceae family provide an essential resource for nutritional, medicinal, and cultivational studies of the economically important star-fruit plant.