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Auxin Response Factors (ARFs) make up a plant-specific transcription factor family that mainly couples perception of the phytohormone, auxin, and gene expression programs and plays an important and multi-faceted role during plant growth and development. Lemongrass (Cymbopogon flexuosus) is a representative Cymbopogon species widely used in gardening, beverages, fragrances, traditional medicine, and heavy metal phytoremediation. Biomass yield is an important trait for several agro-economic purposes of lemongrass, such as landscaping, essential oil production, and phytoremediation. Therefore, we performed gene mining of CfARFs and identified 26 and 27 CfARF-encoding genes in each of the haplotype genomes of lemongrass, respectively. Phylogenetic and domain architecture analyses showed that CfARFs can be divided into four groups, among which groups 1, 2, and 3 correspond to activator, repressor, and ETTN-like ARFs, respectively. To identify the CfARFs that may play major roles during the growth of lemongrass plants, RNA-seq was performed on three tissues (leaf, stem, and root) and four developmental stages (3-leaf, 4-leaf, 5-leaf. and mature stages). The expression profiling of CfARFs identified several highly expressed activator and repressor CfARFs and three CfARFs (CfARF3, 18, and 35) with gradually increased levels during leaf growth. Haplotype-resolved transcriptome analysis revealed that biallelic expression dominance is frequent among CfARFs and contributes to their gene expression patterns. In addition, co-expression network analysis identified the modules enriched with CfARFs. By establishing orthologous relationships among CfARFs, sorghum ARFs, and maize ARFs, we showed that CfARFs were mainly expanded by whole-genome duplications, and that the duplicated CfARFs might have been divergent due to differential expression and variations in domains and motifs. Our work provides a detailed catalog of CfARFs in lemongrass, representing a first step toward characterizing CfARF functions, and may be useful in molecular breeding to enhance lemongrass plant growth.
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Cymbopogon , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos , Filogenia , Proteínas de Plantas , Cymbopogon/genética , Cymbopogon/metabolismo , Cymbopogon/crescimento & desenvolvimento , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Desenvolvimento Vegetal/genética , Reguladores de Crescimento de Plantas/metabolismo , Perfilação da Expressão Gênica , HaplótiposRESUMO
Evidence shows that tropomodulin 1 (TMOD1) is a powerful diagnostic marker in the progression of several cancer types. However, the regulatory mechanism of TMOD1 in tumor progression is still unclear. Here, we showed that TMOD1 was highly expressed in acute myeloid leukemia (AML) specimens, and TMOD1-silencing inhibited cell proliferation by inducing autophagy in AML THP-1 and MOLM-13 cells. Mechanistically, the C-terminal region of TMOD1 directly bound to KPNA2, and TMOD1-overexpression promoted KPNA2 ubiquitylation and reduced KPNA2 levels. In contrast, TMOD1-silencing increased KPNA2 levels and facilitated the nuclear transfer of KPNA2, then subsequently induced autophagy and inhibited cell proliferation by increasing the nucleocytoplasmic transport of p53 and AMPK activation. KPNA2/p53 inhibitors attenuated autophagy induced by silencing TMOD1 in AML cells. Silencing TMOD1 also inhibited tumor growth by elevating KPNA2-mediated autophagy in nude mice bearing MOLM-13 xenografts. Collectively, our data demonstrated that TMOD1 could be a novel therapeutic target for AML treatment.
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BACKGROUND: Chronic atrophic gastritis (CAG) is a global digestive system disease and one of the important causes of gastric cancer. The incidence of CAG has been increasing yearly worldwide. PURPOSE: This article reviews the latest research on the common causes and future therapeutic targets of CAG as well as the pharmacological effects of corresponding clinical drugs. We provide a detailed theoretical basis for further research on possible methods for the treatment of CAG and reversal of the CAG process. RESULTS: CAG often develops from chronic gastritis, and its main pathological manifestation is atrophy of the gastric mucosa, which can develop into gastric cancer. The drug treatment of CAG can be divided into agents that regulate gastric acid secretion, eradicate Helicobacter. pylori (H. pylori), protect gastric mucous membrane, or inhibit inflammatory factors according to their mechanism of action. Although there are limited specific drugs for the treatment of CAG, progress is being made in defining the pathogenesis and therapeutic targets of the disease. Growing evidence shows that NF-κB, PI3K/AKT, Wnt/ ß-catenin, MAPK, Toll-like receptors (TLRs), Hedgehog, and VEGF signaling pathways play an important role in the development of CAG.
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Gastrite Atrófica , Transdução de Sinais , Humanos , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/microbiologia , Gastrite Atrófica/patologia , Gastrite Atrófica/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Doença Crônica , Helicobacter pylori/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologiaRESUMO
Cell surface proteins are responsible for many crucial physiological roles, and they are also the major category of drug targets as the majority of therapeutics target membrane proteins on the surface of cells to alter cellular signaling. Despite its great significance, ligand discovery against membrane proteins has posed a great challenge mainly due to the special property of their natural habitat. Here, we design a new chemical proteomic probe OPA-S-S-alkyne that can efficiently and selectively target the lysines exposed on the cell surface and develop a chemical proteomics strategy for global analysis of surface functionality (GASF) in living cells. In total, we quantified 2639 cell surface lysines in Hela cell and several hundred residues with high reactivity were discovered, which represents the largest dataset of surface functional lysine sites to date. We discovered and validated that hyper-reactive lysine residues K382 on tyrosine kinase-like orphan receptor 2 (ROR2) and K285 on Endoglin (ENG/CD105) are at the protein interaction interface in co-crystal structures of protein complexes, emphasizing the broad potential functional consequences of cell surface lysines and GASF strategy is highly desirable for discovering new active and ligandable sites that can be functionally interrogated for drug discovery.
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Lisina , Proteômica , Humanos , Lisina/metabolismo , Células HeLa , Ligantes , EndoglinaRESUMO
Protein modification by lipid-derived electrophiles (LDEs) is associated with various signaling pathways. Among these LDEs, 4-hydroxy-2-nonenal (HNE) is the most toxic, and protein modified with HNE has been linked to various diseases, including Alzheimer's and Parkinson's. However, due to their low abundance, in-depth profiling of HNE modifications still presents challenges. This study introduces a novel strategy utilizing reversible thiazolidine chemistry to selectively capture HNE-modified proteins and a palladium-mediated cleavage reaction to release them. Thousands of HNE-modified sites in different cell lines were identified. Combined with ABPP, we discovered a set of HNE-sensitive sites that offer a new tool for studying LDE modifications in proteomes.
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Aldeídos , Processamento de Proteína Pós-Traducional , Tiazolidinas , Aldeídos/metabolismo , Proteoma/metabolismo , Peroxidação de LipídeosRESUMO
The objective is to assess the anti-inflammatory effect of Tao Hong Si Wu Tang combined with anti-PD-1 in a mouse model of COPD combined with lung cancer, elucidating its mechanism through modulation of PD-1/PD-L binding, regulation of Th1/Th2 and Th17/Treg balance, inhibition of IL-4 and IL-17, and promotion of IFN-γ and TGF-ß levels in peripheral blood. One hundred male C57/BL6 mice were randomly allocated to five groups: A (blank control), B (model control), C (THSW), D (anti-PD-1), and E (THSW + anti-PD-1), with 20 mice in each group. The COPD model was induced using fumigation and LPS intra-airway drip, followed by the establishment of lung cancer by Lewis cell inoculation. Treatment groups received Tao Hong Si Wu Tang or/and PD-1 monoclonal antibody. Various indicators were assessed, including macroscopic observation, HE staining of lung tissue, ELISA for cytokines, flow cytometry for cell proportions, and immunohistochemistry/western blotting for protein expression. Lung tissue analysis revealed significant differences between groups, with marked tumor formation observed in groups B-E. Serum levels of IL-4, IFN-γ, IL-17, and TGF-ß were significantly altered, along with changes in CD4 + T/CD8 + T ratio and cytokine-producing cell populations. Expression levels of key proteins were also significantly affected across treatment groups. Tao Hong Si Wu Tang demonstrated anti-inflammatory effects comparable to anti-PD-1, potentially through modulation of PD-1/PD-L binding, correction of Th1/Th2 and Th17/Treg imbalance, and modulation of cytokine levels. These findings suggest a role for Tao Hong Si Wu Tang in ameliorating inflammation and immune dysregulation in COPD combined with lung cancer.
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Compensating for the intrinsic attosecond chirp (atto-chirp) of wideband high-order harmonics in the water window region is a significant challenge, in order to obtain isolated attosecond pulses (IAPs) with a width of tens of attoseconds (as). Here, we propose to realize the generation of IAP with duration as short as 20 as, central energy of 365 eV, and bandwidth exceeding 150 eV from chirp-free high harmonics generated by a four-color driving laser, without the necessity for atto-chirp compensation with natural materials. Unlike any other gating methods that an IAP arises from only one electron ionization event, we take advantage of the interference between harmonic radiation produced by multiple ionizing events. We further demonstrate that such chirp-free short IAP survives after taking account of macroscopic propagation effects. Given that the synthesized multicolor laser field can also effectively increase the harmonic flux, this work provides a practical way for experiments to generate the broad bandwidth chirp-free IAPs in the water window region.
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Complicações Neoplásicas na Gravidez , Neoplasias do Colo do Útero , Humanos , Feminino , Gravidez , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Complicações Neoplásicas na Gravidez/cirurgia , Complicações Neoplásicas na Gravidez/patologia , Adulto , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologiaRESUMO
BACKGROUND: Currently, there is no universally accepted standard treatment for ocular myasthenia gravis (OMG) in children. We aimed to investigate the possible proper regimens and timing of treatment for pediatric OMG cases based on the clinical manifestations: OMG with ptosis only and OMG with other features. METHODS: One hundred and forty two OMG cases attended at the Department of Pediatrics, Xiangya Hospital, Central South University, from 2010 to 2019 were included, and information from medical records was reviewed and recorded. Comparisons of clinical characteristics between patients with OMG with ptosis only and patients with OMG with other features as well as between patients treated with glucocorticoid (GC) within or after six months from disease onset were performed. RESULTS: OMG with other features constituted about 54.9% of the cases, and 66.2% of the patients achieved optimal outcome. Patients with OMG with ptosis only responded to pyridostigmine alone more than patients with OMG with other features who required several therapies (P < 0.001). Patients with OMG with ptosis only had a larger proportion of optimal outcome than the patients with OMG with other features (P = 0.002), and the difference remained significant even when the individual outcome groups were compared (P < 0.001). Patients who received GC within six months had a greater proportion of optimal outcome than those who received it after six months (P < 0.001). CONCLUSIONS: Although OMG with other features is a more common subtype of OMG, it is also more severe than OMG with ptosis only. An earlier addition of GC leads to optimal outcome.
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Blefaroptose , Miastenia Gravis , Humanos , Criança , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Blefaroptose/tratamento farmacológico , Blefaroptose/etiologia , Brometo de Piridostigmina/uso terapêutico , Glucocorticoides/uso terapêutico , Estudos RetrospectivosRESUMO
Terpenoids are a class of structurally complex, naturally occurring compounds found predominantly in plant, animal, and microorganism secondary metabolites. Classical terpenoids typically have carbon atoms in multiples of five and follow well-defined carbon skeletons, whereas noncanonical terpenoids deviate from these patterns. These noncanonical terpenoids often result from the methyltransferase-catalyzed methylation modification of substrate units, leading to irregular carbon skeletons. In this comprehensive review, various activities and applications of these noncanonical terpenes have been summarized. Importantly, the review delves into the biosynthetic pathways of noncanonical terpenes, including those with C6, C7, C11, C12, and C16 carbon skeletons, in bacteria and fungi host. It also covers noncanonical triterpenes synthesized from non-squalene substrates and nortriterpenes in Ganoderma lucidum, providing detailed examples to elucidate the intricate biosynthetic processes involved. Finally, the review outlines the potential future applications of noncanonical terpenoids. In conclusion, the insights gathered from this review provide a reference for understanding the biosynthesis of these noncanonical terpenes and pave the way for the discovery of additional unique and novel noncanonical terpenes. KEY POINTS: â¢The activities and applications of noncanonical terpenoids are introduced. â¢The noncanonical terpenoids with irregular carbon skeletons are presented. â¢The microbial biosynthesis of noncanonical terpenoids is summarized.
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Terpenos , Triterpenos , Animais , Carbono , Metiltransferases , Processamento de Proteína Pós-TraducionalRESUMO
Home-based movement neuro-rehabilitation is quite necessary when the patient goes back home from hospital. Due to lack of supervision from doctors, rehabilitation at home is often forgotten. As an alternate to doctor-supervision, in this research, we explore the wireless device-free localization technique to assist the rehabilitation procedure. The localization technique can judge whether the patient is near the rehabilitation equipment and even obtain the movement trajectory. The most challenging problem in the wireless device-free localization system is that the received-signal-strength (RSS) of the electromagnetic-wave is unpredictable, which increases the localization error. How to select the informative RSS is pretty important. This research proposes a new criterion (i.e., fluctuation-level) to select the informative RSS. Experimental results show the effectiveness of the proposed fluctuation-level in reducing the localization error.
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Medium-sized lactones are important structural units, but their synthesis remains a great challenge. Herein, we report I2/CF3CO2Ag-mediated iodolactonization of allenoic acids to synthesize various 6- to 9-membered ring vinylic iodolactones in 16-89% yield. This protocol not only develops a new cyclization strategy of allenoic acids, but also provides highly functionalized medium-sized lactones containing alkene and halogen groups.
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Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.
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Chalconas , Melanoma , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Melanoma/metabolismo , Diferenciação Celular , Via de Sinalização Wnt , Serina-Treonina Quinases TOR/metabolismo , Proliferação de Células , Movimento Celular , Linhagem Celular TumoralRESUMO
With the continuous deepening of genetic research on neurodevelopmental disorders (NDDs), more patients have been identified the causal or candidate genes. However, it is still urgent needed to increase the sample size to confirm the associations between variants and clinical manifestations. We previously performed molecular inversion probe sequencing of autism spectrum disorder (ASD) candidate genes in 1543 ASD patients. In this study, we used the same method to detect de novo variants (DNVs) in 665 NDD patients with intellectual disability (ID) and/or epilepsy (EP) for genetic analysis and diagnosis. We compared findings from ID/EP and ASD patients to improve our understanding of different subgroups of NDDs. We identified 72 novel variants and 39 DNVs. A totally of 5.71 % (38/665) of the patients were genetically diagnosed by this sequencing strategy. ID/EP patients demonstrated a higher prevalence of likely gene disruptive DNVs in ASD genes than the healthy population. Regarding high-risk genes, SCN1A and CKDL5 were more frequently mutated in ID/EP patients than in ASD patients. Our data provide an overview of the mutation burden in ID/EP patients from the perspective of high risk ASD genes, indicating the differences and association of NDDs subgroups.
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Transtorno do Espectro Autista , Epilepsia , Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Humanos , Transtorno do Espectro Autista/genética , Transtornos do Neurodesenvolvimento/genética , Deficiência Intelectual/genética , Epilepsia/genética , Predisposição Genética para DoençaRESUMO
BACKGROUND: Although partial nephrectomy has become the gold standard for T1 renal tumors whenever technically feasible, simple enucleation has shown superior results. To the best of our knowledge, no randomized controlled trials comparing these two surgical approaches have been published. OBJECTIVE: To compare the surgical margin status for robot-assisted simple enucleation (RASE) and standard robot-assisted partial nephrectomy (sRAPN) for clinical T1 renal tumors. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective, randomized, controlled, noninferiority trial. A total of 380 patients aged 18-80 yr with newly diagnosed, sporadic, unilateral clinical T1 renal tumors (RENAL score <10) were enrolled and randomized to RASE or sRAPN. The primary endpoint was the positive surgical margin (PSM) rate, with a noninferiority margin of 7.5% set. The study was registered on ClinicalTrials.gov (NCT03624673). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We defined noninferiority for RASE versus standard RAPN as an upper 95% confidence interval (CI) bound of <7.5% for the difference in the proportion of patients with a PSM. RESULTS AND LIMITATIONS: A cohort of 380 patients was enrolled and randomly assigned to RASE (n = 190) or sRAPN (n = 190). On intention-to-treat analysis for patients with malignant tumors, 2.3% of patients in the RASE group and 3.0% in the sRAPN group had a PSM. The RASE group showed noninferiority to the sRAPN group within a 7.5% margin (difference -0.7%, 95% CI -4.0% to 2.7%). Per-protocol analysis also demonstrated noninferiority of RASE. The RASE group had a shorter median operative time (145 vs 155 min; p = 0.018) and a lower rate of tumor bed suturing (8.9% vs 43%; p < 0.001) in comparison to the sRAPN group. Estimated blood loss was considerably lower in the sRAPN group than in the RASE group (p = 0.046). The rate of recurrence did not differ between the groups (p > 0.9). CONCLUSIONS: RASE for the management of low- to intermediate-complexity tumors is noninferior to sRAPN in terms of the PSM rate. Long-term follow-up is needed to draw conclusions regarding oncological outcomes. PATIENT SUMMARY: We carried out a trial to compare simple tumor enucleation versus partial nephrectomy for renal tumors. The outcome we assessed was the proportion of patients with a positive surgical margin. Our results show that simple tumor enucleation is not inferior to partial nephrectomy for this outcome. Longer follow-up is needed to assess other cancer control outcomes.
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Neoplasias Renais , Robótica , Humanos , Margens de Excisão , Estudos Prospectivos , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Nefrectomia/métodosRESUMO
Objective. Bladder cancer is a common malignant urinary carcinoma, with muscle-invasive and non-muscle-invasive as its two major subtypes. This paper aims to achieve automated bladder cancer invasiveness localization and classification based on MRI.Approach. Different from previous efforts that segment bladder wall and tumor, we propose a novel end-to-end multi-scale multi-task spatial feature encoder network (MM-SFENet) for locating and classifying bladder cancer, according to the classification criteria of the spatial relationship between the tumor and bladder wall. First, we built a backbone with residual blocks to distinguish bladder wall and tumor; then, a spatial feature encoder is designed to encode the multi-level features of the backbone to learn the criteria.Main Results. We substitute Smooth-L1 Loss with IoU Loss for multi-task learning, to improve the accuracy of the classification task. By learning two datasets collected from bladder cancer patients at the hospital, the mAP, IoU, Acc, Sen and Spec are used as the evaluation metrics. The experimental result could reach 93.34%, 83.16%, 85.65%, 81.51%, 89.23% on test set1 and 80.21%, 75.43%, 79.52%, 71.87%, 77.86% on test set2.Significance. The experimental result demonstrates the effectiveness of the proposed MM-SFENet on the localization and classification of bladder cancer. It may provide an effective supplementary diagnosis method for bladder cancer staging.
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Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Bexiga Urinária/patologiaRESUMO
While diagnosing multiple lesion regions in chest X-ray (CXR) images, radiologists usually apply pathological relationships in medicine before making decisions. Therefore, a comprehensive analysis of labeling relationships in different data modes is essential to improve the recognition performance of the model. However, most automated CXR diagnostic methods that consider pathological relationships treat different data modalities as independent learning objects, ignoring the alignment of pathological relationships among different data modalities. In addition, some methods that use undirected graphs to model pathological relationships ignore the directed information, making it difficult to model all pathological relationships accurately. In this paper, we propose a novel multi-label CXR classification model called MRChexNet that consists of three modules: a representation learning module (RLM), a multi-modal bridge module (MBM) and a pathology graph learning module (PGL). RLM captures specific pathological features at the image level. MBM performs cross-modal alignment of pathology relationships in different data modalities. PGL models directed relationships between disease occurrences as directed graphs. Finally, the designed graph learning block in PGL performs the integrated learning of pathology relationships in different data modalities. We evaluated MRChexNet on two large-scale CXR datasets (ChestX-Ray14 and CheXpert) and achieved state-of-the-art performance. The mean area under the curve (AUC) scores for the 14 pathologies were 0.8503 (ChestX-Ray14) and 0.8649 (CheXpert). MRChexNet effectively aligns pathology relationships in different modalities and learns more detailed correlations between pathologies. It demonstrates high accuracy and generalization compared to competing approaches. MRChexNet can contribute to thoracic disease recognition in CXR.
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Aprendizagem , Doenças Torácicas , Humanos , Raios X , Doenças Torácicas/diagnóstico por imagem , Área Sob a Curva , Tomada de DecisõesRESUMO
The traditional Chinese medicine (TCM) Rehmanniae Radix (RR) refers to the fresh or dried root tuber of the plant Rehmannia glutinosa Libosch of the family Scrophulariaceae. As a traditional Chinese herbal medicine (CHM), it possesses multiple effects, including analgesia, sedation, anti-inflammation, antioxidation, anti-tumor, immunomodulation, cardiovascular and cerebrovascular regulation, and nerve damage repair, and it has been widely used in clinical practice. In recent years, scientists have extensively studied the active components and pharmacological effects of RR. Active ingredients mainly include iridoid glycosides (such as catalpol and aucuboside), phenylpropanoid glycosides (such as acteoside), other saccharides, and unsaturated fatty acids. In addition, the Chinese patent medicine (CPM) and Chinese decoction related to RR have also become major research subjects for TCM practitioners; one example is the Bolus of Six Drugs, which includes Rehmannia, Lily Bulb and Rehmannia Decoction, and Siwu Decoction. This article reviews recent literature on RR; summarizes the studies on its chemical constituents, pharmacological effects, and clinical applications; and analyzes the progress and limitations of current investigations to provide reference for further exploration and development of RR.
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Medicamentos de Ervas Chinesas , Rehmannia , Humanos , Medicina Tradicional Chinesa , Extratos Vegetais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Glicosídeos IridoidesRESUMO
Lymph node (LN) metastasis is one of the key prognostic factors in bladder cancer, but its underlying mechanisms remain unclear. Here, we found that elevated expression of WD repeat domain 4 (WDR4) in bladder cancer correlated with worse prognosis. WDR4 can promote the LN metastasis and proliferation of bladder cancer cells. Mechanistic studies showed that WDR4 can promote the nuclear localization of DEAD-box helicase 20 (DDX20) and act as an adaptor to bind DDX20 and Early growth response 1 (Egr1), thereby inhibiting Egr1-promoted transcriptional expression of arrestin beta 2 (ARRB2) and ultimately contributing to the progression of bladder cancer. Immunohistochemical analysis confirmed that WDR4 expression is also an independent predictor of LN metastasis in bladder cancer. Our results reveal a novel mechanism of LN metastasis and progression in bladder cancer and identify WDR4 as a potential therapeutic target for metastatic bladder cancer.
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Aging is a pressing global health issue that is linked to various diseases, such as diabetes and Alzheimer's disease. It is well known that glycation plays a pathological role in the aging process and age-related diseases. Thus, it is of great significance to discover protein glycation at an early stage for monitoring and intervention in the aging process. However, the endogenous age-related early-stage glycated proteome remains insufficiently profiled. To address this research gap, our study focuses on assessing glycated proteomics profiles in the serum of mice. We employ a robust and quantitative strategy previously developed by our team, to analyze endogenous glycated proteome in serum samples of 4 age groups of mice (10 weeks, 16 weeks, 48 weeks and 80 weeks). In total, 2959 endogenous glycated peptides corresponding to 296 serum proteins are identified from 48 runs of serum samples from 16 mice across the four age groups. By comparing these glycated peptides between adjacent age groups, we discover 49 glycated peptides from 35 proteins that show significant upregulation between the 48-week and 80-week age groups. Furthermore, we identify 10 glycated proteins (or protein groups) that are significantly upregulated only between the 48-week and 80-week age groups, including lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein A-II (Apo A-II). These novel findings provide unique signatures for understanding the aging process and age-related diseases. By shedding light on the early-stage glycated proteome, our study contributes valuable insights that may have implications for future interventions and therapeutic approaches.