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The small molecule epiberberine (EPI) is a natural alkaloid with versatile bioactivities against several diseases including cancer and bacterial infection. EPI can induce the formation of a unique binding pocket at the 5' side of a human telomeric G-quadruplex (HTG) sequence with four telomeric repeats (Q4), resulting in a nanomolar binding affinity (KD approximately 26 nM) with significant fluorescence enhancement upon binding. It is important to understand (1) how EPI binding affects HTG structural stability and (2) how enhanced EPI binding may be achieved through the engineering of the DNA binding pocket. In this work, the EPI-binding-induced HTG structure stabilization effect was probed by a peptide nucleic acid (PNA) invasion assay in combination with a series of biophysical techniques. We show that the PNA invasion-based method may be useful for the characterization of compounds binding to DNA (and RNA) structures under physiological conditions without the need to vary the solution temperature or buffer components, which are typically needed for structural stability characterization. Importantly, the combination of theoretical modeling and experimental quantification allows us to successfully engineer Q4 derivative Q4-ds-A by a simple extension of a duplex structure to Q4 at the 5' end. Q4-ds-A is an excellent EPI binder with a KD of 8 nM, with the binding enhancement achieved through the preformation of a binding pocket and a reduced dissociation rate. The tight binding of Q4 and Q4-ds-A with EPI allows us to develop a novel magnetic bead-based affinity purification system to effectively extract EPI from Rhizoma coptidis (Huang Lian) extracts.
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Berberina , G-Cuádruplex , Berberina/química , Berberina/análogos & derivados , Berberina/farmacología , Humanos , ADN/química , Ácidos Nucleicos de Péptidos/químicaRESUMEN
Proper transcription regulation by key transcription factors, such as IRF3, is critical for anti-viral defense. Dynamics of enhancer activity play important roles in many biological processes, and epigenomic analysis is used to determine the involved enhancers and transcription factors. To determine new transcription factors in anti-DNA-virus response, we have performed H3K27ac ChIP-Seq and identified three transcription factors, NR2F6, MEF2D and MAFF, in promoting HSV-1 replication. NR2F6 promotes HSV-1 replication and gene expression in vitro and in vivo, but not dependent on cGAS/STING pathway. NR2F6 binds to the promoter of MAP3K5 and activates AP-1/c-Jun pathway, which is critical for DNA virus replication. On the other hand, NR2F6 is transcriptionally repressed by c-Jun and forms a negative feedback loop. Meanwhile, cGAS/STING innate immunity signaling represses NR2F6 through STAT3. Taken together, we have identified new transcription factors and revealed the underlying mechanisms involved in the network between DNA viruses and host cells.
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Herpesvirus Humano 1 , Inmunidad Innata , Humanos , Animales , Herpesvirus Humano 1/inmunología , Ratones , Replicación Viral , Herpes Simple/inmunología , Herpes Simple/virología , Herpes Simple/metabolismo , Transducción de Señal , Células HEK293 , Proteínas RepresorasRESUMEN
Background: There have been no reports about the application of random survival forest (RSF) model to predict disease progression of HIV-associated B-cell lymphoma. Methods: A total of 44 patients with HIV-associated B-cell lymphoma who were referred to Nanjing Second Hospital from 2012 to 2019 were included. The RSF model was used to find predictors of survival, and the results of the RSF model were compared with those of the Cox model. The data were analyzed using R software (version 4.1.1). Results: One-, 2-, and 3-year survival rates were 74.5%, 57.7%, and 48.6%, respectively, and the median survival was 59.0 months. The first 3 most important predictors of survival included lactate dehydrogenase (LDH), absolute monocyte count (AMC), and white blood cells (WBCs) count. The median survival of high-risk patients was only 4.0 months. Areas under the curve (AUCs) of the RSF model remained at more than 0.90 at 1, 2, and 3 years. The RSF model displayed a lower prediction error rate (21.9%) than the Cox model (25.4%). Conclusions: Lactate dehydrogenase, AMC, and WBCs count are the most important prognostic predictors for patients with HIV-associated B-cell lymphoma. Much larger prospective and/or multicentre studies are required to validtae this RSF model.
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A bowl-shaped phosphangulene-protected cubic Cu58 nanocluster has been synthesized. The structure was determined by X-ray crystallography and further analyzed by multiple techniques. The phosphangulenes not only enable ligand substitutions with triphenylphosphines in a cluster-to-cluster transformation way, but also facilitate inter-cluster interactions with fullerenes. These interactions further influence the entirety's photocurrent response and ability to liberate hydrogen when stimulated by light.
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PURPOSE: The present study aimed to explore the potential components and mechanisms of Rhodiola rosea-Euonymus alatus drug pair (TY) that ameliorate rheumatoid arthritis (RA). METHODS: The main active components, core targets, and important pathways of TY against RA were predicted by network pharmacology analysis. The binding activity between the main active components and the core targets was verified by the molecular docking technique. Collagen-induced arthritis (CIA) rat model and tumor necrosis factor (TNF)-α-induced fibroblast-like synovial cells in human RA (HFLS-RA) model were established, respectively. The core targets were verified by cell counting kit-8 assay, hematoxylin eosin, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot analysis, and the therapeutic effect of TY was evaluated. RESULTS: A total of 18 possible components and 34 core targets were obtained by network pharmacology, among which inflammatory response, phosphatidylinositide 3-kinases (PI3K)-AKT and MAPK pathways were involved in the therapeutic effect of TY on RA. The results of molecular docking showed that kaempferol and quercetin had high binding affinity to interleukin (IL)-1ß, IL-6, matrix metalloproteinase (MMP)9, and TNF-α. In vivo and in vitro experiments showed that TY dose-dependently inhibited the proliferation of HFLS-RA cells induced by TNF-α, and significantly reduced the paw swelling and arthritis scores in CIA rats. At the same time, TY inhibited the production of inflammatory factors in CIA rat serum and TNF-α-induced HFLS-RA cells. It also decreased the expression of PI3K, phospho-protein kinase B, MMP1, MMP3, MMP9, and increased the protein and mRNA levels of tissue inhibitors of MMPs (TIMP)1 in synovial tissue. CONCLUSION: TY can inhibit the PI3K/AKT signaling pathway and regulate the balance between MMPs and TIMP, thus playing a therapeutic role in RA.
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Artritis Experimental , Artritis Reumatoide , Euonymus , Rhodiola , Humanos , Ratas , Animales , Euonymus/metabolismo , Rhodiola/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Proto-Oncogénicas c-akt , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Metaloproteinasas de la Matriz/uso terapéuticoRESUMEN
BACKGROUND: Enhancer dysregulation is one of the important features for cancer cells. Enhancers enriched with H3K4me3 have been implicated to play important roles in cancer. However, their detailed features and regulatory mechanisms have not been well characterized. RESULTS: Here, we profile the landscape of H3K4me3-enriched enhancers (m3Es) in 43 pairs of colorectal cancer (CRC) samples. M3Es are widely distributed in CRC and averagely possess around 10% of total active enhancers. We identify 1322 gain variant m3Es and 367 lost variant m3Es in CRC. The target genes of the gain m3Es are enriched in immune response pathways. We experimentally prove that repression of CBX8 and RPS6KA5 m3Es inhibits target gene expression in CRC. Furthermore, we find histone methyltransferase MLL1 is responsible for depositing H3K4me3 on the identified Vm3Es. We demonstrate that the transcription factor AP1/JUN interacts with MLL1 and regulates m3E activity. Application of a small chemical inhibitor for MLL1 activity, OICR-9429, represses target gene expression of the identified Vm3Es, enhances anti-tumor immunity and inhibits CRC growth in an animal model. CONCLUSIONS: Taken together, our study illustrates the genome-wide landscape and the regulatory mechanisms of m3Es in CRC, and reveals potential novel strategies for cancer treatment.
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Neoplasias Colorrectales , Histonas , Proteína de la Leucemia Mieloide-Linfoide , Proteínas Proto-Oncogénicas c-jun , Animales , Neoplasias Colorrectales/genética , Elementos de Facilitación Genéticos , Histonas/metabolismo , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Factor de Transcripción AP-1/metabolismo , Humanos , Proteínas Proto-Oncogénicas c-jun/genética , Proteínas Proto-Oncogénicas c-jun/metabolismoRESUMEN
BACKGROUND: Soybean is one of the most important oil crops in the world. The domestication of wild soybean has resulted in significant changes in the seed oil content and seed size of cultivated soybeans. To better understand the molecular mechanisms of seed formation and oil content accumulation, WDD01514 (E1), ZYD00463 (E2), and two extreme progenies (E23 and E171) derived from RILs were used for weighted gene coexpression network analysis (WGCNA) combined with transcriptome analysis. RESULTS: In this study, both seed weight and oil content in E1 and E171 were significantly higher than those in E2 and E23, and 20 DAF and 30 DAF may be key stages of soybean seed oil content accumulation and weight increase. Pathways such as "Photosynthesis", "Carbon metabolism", and "Fatty acid metabolism", were involved in oil content accumulation and grain formation between wild and cultivated soybeans at 20 and 30 DAF according to RNA-seq analysis. A total of 121 oil content accumulation and 189 seed formation candidate genes were screened from differentially expressed genes. WGCNA identified six modules related to seed oil content and seed weight, and 76 candidate genes were screened from modules and network. Among them, 16 genes were used for qRT-PCR and tissue specific expression pattern analysis, and their expression-levels in 33-wild and 23-cultivated soybean varieties were subjected to correlation analysis; some key genes were verified as likely to be involved in oil content accumulation and grain formation. CONCLUSIONS: Overall, these results contribute to an understanding of seed lipid metabolism and seed size during seed development, and identify potential functional genes for improving soybean yield and seed oil quantity.
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Fabaceae , Glycine max , Glycine max/genética , Semillas/genética , Perfilación de la Expresión Génica , Grano Comestible , Aceites de PlantasRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The detailed epigenomic changes during fat accumulation in liver are not clear yet. Here, we performed ChIP-Seq analysis in the liver tissues of high-fat diet and regular chow diet mice and investigated the dynamic landscapes of H3K27ac and H3K9me3 marks on chromatin. We find that the activated typical enhancers marked with H3K27ac are enriched on lipid metabolic pathways in fat liver; however, super enhancers do not change much. The regions covered with H3K9me3 repressive mark seem to undergo great changes, and its peak number and intensity both decrease in fat liver. The enhancers located in lost H3K9me3 regions are enriched in lipid metabolism and inflammatory pathways; and motif analysis shows that they are potential targets for transcription factors involved in metabolic and inflammatory processes. Our study has revealed that H3K9me3 may play an important role during the pathogenesis of NAFLD through regulating the accessibility of enhancers.
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Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/patología , Metabolismo de los Lípidos/genética , Epigénesis GenéticaRESUMEN
Lung cancer is one of the common malignant tumors in the world, and its incidence and mortality is increasing year by year. Interactions between tumor cells and immune cells in the tumor microenvironment(TME) affect tumor proliferation, infiltration, and metastasis. Tumor-associated macrophages(TAMs) are prominent components of TME, and they have dual regulation effects on malignant progression of lung cancer. The number, activity, and function of M2 macrophages are related to the poor prognosis of lung cancer, and M2 macrophages participate in tumor angiogenesis and immune escape. It has been proved that traditional Chinese medicines(TCMs) and their active ingredients can enhance the antitumor effects, reduce the toxicity of chemotherapy and radiotherapy, and prolong the survival rates of patients with cancer. This paper summarized the role of TAMs in the lung cancer initiation and progression, explored the molecular mechanism of TCM in regulating the recruitment, polarization phenotype, activity, and expression of related factors and proteins of TAMs, and discussed related signal pathways in the prevention and treatment of lung cancer based on the TCM theory of "reinforcing healthy qi and eliminating pathogen". This paper is expected to provide new ideas for the immunotherapy of targeted TAMs.
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Neoplasias Pulmonares , Macrófagos Asociados a Tumores , Humanos , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , Medicina Tradicional China , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Macrófagos , Inmunoterapia , Microambiente TumoralRESUMEN
When plates with edge cracks in the rolling process is straightened by cyclic tensile and compressive stress, the tip of edge crack always accompanied by stress concentration, which leads to crack propagation. In this paper, damage parameters are imported into the plate straightening model based on determining the GTN damage parameters of magnesium alloy materials by inverse finite element calibration method, the influence of different straightening process schemes and prefabricated V-shaped crack geometry on crack growth is analyzed through the way of the combination of simulation and straightening experiment. The results show that the peak values of equivalent stress and equivalent strain under each straightening roll appear at the crack tip. The value of longitudinal stress and equivalent stain decrease with the distance to crack tip becomes larger. The peak value of longitudinal stress appears when the crack circumferential angle is about 100°, and the crack tip is easy to form crack propagation; when the plate passes roll 2 and roll 4, the equivalent stress and strain concentration at the crack tip are most obvious; when the reduction reaches a certain degree, the void volume fraction (VVF) reaches the VVF of the material breaking; with the increase of the entrance reduction, the number of VVF at the crack tip which reaches the material fracture increases, and the length of crack propagation increases; the stress concentration at the tip of V-shaped crack with large length-width ratio is obvious, and the VVF is more likely to reach the VVF at the time of material fracture, crack initiates and propagates easily.
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The harvest period of cultivated ginseng is generally 4-6 years. Ginseng flowers (GFs), the nonmedicinal parts, are usually removed every autumn, in which components are generally believed to stay unchanged with the increasing cultivation age. Recently, few documents were reported on the variation of volatile organic compounds (VOCs) and other components about ginseng flowers. This study had an insight into the variation of the chemical constituents with the cultivation ages through the comparison of the volatile organic compounds, gross ginsenosides, crude polysaccharide, and gross proteins of ginseng flowers from 3-, 4-, 5-, and 6-yr-old (GF3, GF4, GF5, and GF6) which were conducted by headspace solid-phase microextraction-gas chromatography-triple quadrupole mass spectrometry (HS-SPME-GC-QQQ/MS) and spectroscopic analysis combined with multivariate statistical analysis, including one-way ANOVA analysis and T test. The results indicated that the crude polysaccharide contents raised significantly depending on cultivation age except 6-yr-old, whereas the gross ginsenosides and the gross protein content were indistinctive. According to the peak intensity of determined VOCs, the contents of most differential compounds arranged in an order from high to low are GF3, GF4, GF5, and GF6, such as the compounds 2-15, 17-19, 22, and 25-26, therefore, they can be inferred that they are important markers to identify the age of GFs. 461 common differential compounds were gained and 26 common volatile organic compounds were identified with RSI >800 and RI and RIx no more than 30, including alcohols (such as 11, 12, and 15), sesquiterpenes (such as 2, 3, and 4), esters (such as 1 and 26), naphthalene and naphthol (such as 7 and 20), which had potential effects on curing Alzheimer's disease, inflammatory diseases, and prostate cancer based on network pharmacology analysis. This paper firstly revealed the variation rules of constitutions of GFs, which may provide a reference for the harvest and making rational application.
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Objective: To explore the curative effect of buttress plate and traditional internal fixation in the treatment of ankle fracture, so as to provide potential reference for the clinical treatment of this disease. Methods: This is a clinical comparative study. The subjects of this study were one hundred patients with ankle fracture treated in Mindong Hospital Affiliated to Fujian Medical University from January 2019 to December 2021. Enrolled patients were randomly divided into the control group and the experimental group. Patients in the control group were treated with traditional internal fixation, and those in the experimental group were provided with buttress plate. Patients were compared in several aspects such as the comprehensive quality of life assessment questionnaire (GQOLI-74), Baird-Jackson score and postoperative complications. Result: The experimental group showed improved Baird-Jackson score after treatment, significantly higher fracture healing rate than that of the control group three months after treatment. Besides, there was no significant difference in the complications between the two groups, with good prognosis after timely treatment. Conclusion: Internal fixation with buttress plate has obvious advantages in the treatment of ankle fractures, which can effectively improve the quality of life and promote the rapid healing of fractures. It is worthy of clinical promotion and application.
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Soybean cyst nematode (SCN, Heterodera glycines, HG) is one of the severe pests in plant-parasitic nematodes, which impairs root development and causes severe losses in soybean production worldwide. Breeding SCN-resistant cultivars is an important measure for securing harvests without affecting the environment, as can be done with pesticides. The majority of genetic resources for plant pest resistances are found in wild or closely related species which are often difficult to use in breeding due to crossing barriers or close linkage with unfavorable agronomic traits. In this study, 12 soybean cultivars were evaluated for their marker haplotype at the rhg1 and Rhg4 SCN resistance loci and their SCN resistance tested against multiple races in environmentally controlled bioassays. The results showed that all 12 cultivars displayed Peking-type resistance marker haplotypes and all of them proved to be resistant to multiple SCN races. These cultivars provide potential for improving H. glycines resistance of soybean as donor parent in breeding and can contribute to reduce SCN field populations as part of a sustainable agriculture management.
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Soybean cyst nematode (SCN) is a serious damaging disease in soybean worldwide. Peking- and PI 88788-type sources of resistance are two most important germplasm used in breeding resistant soybean cultivars against this disease. However, until now, no comparisons of constitutive resistances to soybean cyst nematode between these two types of sources had been conducted, probably due to the influences of different backgrounds. In this study, we used pooled-sample analysis strategy to minimize the influence of different backgrounds and directly compared the molecular mechanisms underlying constitutive resistance to soybean cyst nematode between these two types of sources via transcriptomic and metabolomic profilings. Six resistant soybean accessions that have identical haplotypes as Peking at Rgh1 and Rhg4 loci were pooled to represent Peking-type sources. The PI88788-type and control pools were also constructed in a same way. Through transcriptomic and metabolomics anaylses, differentially expressed genes and metabolites were identified. The molecular pathways involved in the metabolism of toxic metabolites were predicted to play important roles in conferring soybean cyst nematode resistance to soybean. Functions of two resistant candidate genes were confirmed by hairy roots transformation methods in soybean. Our studies can be helpful for soybean scientists to further learn about the molecular mechanism of resistance to soybean cyst nematode in soybean.
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Abnormality of enhancer regulation has emerged as one of the critical features for cancer cells. KDM5C is a histone H3K4 demethylase and frequently mutated in several types of cancer. It is critical for H3K4me3 and activity of enhancers, but its regulatory mechanisms remain elusive. Here, we identify TRIM11 as one ubiquitin E3 ligase for KDM5C. TRIM11 interacts with KDM5C, catalyzes K48-linked ubiquitin chain on KDM5C, and promotes KDM5C degradation through proteasome. TRIM11 deficiency in an animal model represses the growth of breast tumor and stabilizes KDM5C. In breast cancer patient tissues, TRIM11 is highly expressed and KDM5C is lower expressed, and their expression is negatively correlated. Mechanistically, TRIM11 regulates the enhancer activity of genes involved in cell migration and immune response by targeting KDM5C. TRIM11 and KDM5C regulate MCAM expression and cell migration through targeting H3K4me3 on MCAM enhancer. Taken together, our study reveals novel mechanisms for enhancer regulation during breast cancer tumorigenesis and development.
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Histonas , Neoplasias , Animales , Carcinogénesis/genética , Línea Celular Tumoral , Histona Demetilasas/genética , Histona Demetilasas/metabolismo , Histonas/genética , Histonas/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas/metabolismoRESUMEN
BACKGROUND: Limited information exists comparing the perioperative complications of the different inflammatory arthropathies (IAs) after total hip arthroplasty (THA). Our study was aimed to (1) compare perioperative complications and (2) determine the most common complications between the different IA subtypes compared with patients with primary osteoarthritis (OA) undergoing primary THA and (3) find whether the difference in postoperative complications also exists between different IA after THA. METHODS: The Nationwide Inpatient Sample (NIS) was used to identify patients with Rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis (AS), and primary OA undergoing unilateral THA between 2005 and 2014. Preoperative diagnosis, comorbidities, and postoperative complications were determined using the International Classification of Disease Clinical Modification version 9 codes. The prevalence of perioperative complications was compared between patients with IA and primary OA and between patients with different IA. RESULTS: When compared with patients with primary OA, patients with RA had significantly more postoperative surgical and medical complications. Yet there are just several medical complications differences exist between PA and primary OA or AS and primary OA, including stroke and acute renal failure for psoriatic arthritis and urinary tract infection and pneumonia for AS. What is more, there were also several differences in perioperative medical complications seen in patients with different IA. CONCLUSION: Except for patients with RA, the differences in perioperative complications was small between patients with IA and primary OA and between patients with different types of IA.
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Artritis Psoriásica , Artritis Reumatoide , Artroplastia de Reemplazo de Cadera , Osteoartritis de la Cadera , Osteoartritis , Espondilitis Anquilosante , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Artritis Psoriásica/epidemiología , Artritis Psoriásica/cirugía , Artritis Psoriásica/complicaciones , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/cirugía , Artritis Reumatoide/epidemiología , Artritis Reumatoide/cirugía , Artritis Reumatoide/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Osteoartritis/epidemiología , Osteoartritis/cirugía , Osteoartritis/complicaciones , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Cadera/cirugía , Osteoartritis de la Cadera/diagnósticoRESUMEN
We conducted this retrospective study to identify potential clinical, polysomnographic, and cephalometric predictors for the treatment outcomes of a tongue-beaded oral appliance (OA) in children with obstructive sleep apnea syndrome (OSAS). In total, 63 patients50 boys and 13 girls ranging in age from 4 to 16 yearsunderwent OA treatment nightly for at least 6 months. A baseline digital lateral cephalometric radiograph was obtained for each patient. Multivariate logistic regression analysis was performed to examine predictors for the treatment outcome based on the clinical and cephalometric measurements. Overall, 28 patients responded to the treatment (post-treatment improvement > 50% or apnea−hypopnea index (AHI) < 1/h), and 35 did not (post-treatment improvement < 50% and AHI ≥ 1/h). Significantly larger cranial base angle (SNBa), smaller lower gonial angle (LGo Angle), and shorter length of anterior cranial base (SN) were found in responders. Smaller lower gonial angle (LGo Angle) and smaller anterior cranial base (SN) predict a favorable outcome for pediatric OSAS using a tongue-beaded OA. This finding will equip practitioners with additional insights when selecting suitable candidates for OA therapy in pediatric patients.
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The continuous evolution and spread of virulent forms of the soybean cyst nematode (SCN) driven by the environment and anthropogenic intervention is a serious threat to the soybean production worldwide, including China. Especially in China, the implemented measures to control SCN are insufficient for sustainable agricultural development yet. We summarized our knowledge about the spread and spatial distribution of SCN in China and the virulence diversity in the main soybean growing areas. To reveal the genetic relatedness and diversity of SCN populations, we re-sequenced 53 SCN genomes from the Huang-Huai Valleys, one of the two main soybean growing areas in China. We identified spreading patterns linked to the local agroecosystems and topographies. Moreover, we disclosed the first evidence for the selection of complex virulence in the field even under low selection pressure in an example from North Shanxi. SCN is present in all soybean growing areas in China but SCN susceptible cultivars are still largely grown indicating that SCN-related damage and financial loss have not received the attention they deserve yet. To prevent increasing yield losses and to improve the acceptance of resistant cultivars by the growers, we emphasized that it is time to accelerate SCN resistance breeding, planting resistant cultivars to a larger extent, and to support farmers to implement a wider crop rotation for sustainable development of the soybean production in China.
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Enhancer is one kind of cis-elements regulating gene transcription, whose activity is tightly controlled by epigenetic enzymes and histone modifications. Active enhancers are classified into typical enhancers, super-enhancers and over-active enhancers, according to the enrichment and location of histone modifications. Epigenetic factors control the level of histone modifications on enhancers to determine their activity, such as histone methyltransferases and acetylases. Transcription factors, cofactors and mediators co-operate together and are required for enhancer functions. In turn, abnormalities in these trans-acting factors affect enhancer activity. Recent studies have revealed enhancer dysregulation as one of the important features for cancer. Variations in enhancer regions and mutations of enhancer regulatory genes are frequently observed in cancer cells, and altering the activity of onco-enhancers is able to repress oncogene expression, and suppress tumorigenesis and metastasis. Here we summarize the recent discoveries about enhancer regulation in cancer and discuss their potential application in diagnosis and treatment.
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Elementos de Facilitación Genéticos , Neoplasias , Epigenómica , Código de Histonas , Humanos , Neoplasias/genética , Factores de Transcripción/genéticaRESUMEN
Tacrolimus is an important immunosuppressant produced by microbial fermentation. In this study, a modified nanoscale polymeric adsorbent, Ag+-exchanged resin, was prepared and studied for the preparative separation and purification of tacrolimus from fermentation broth of Streptomyces tsukubaensis. The performance and absorption characteristics of the modified nanoscale polymeric adsorbent namely Ag-NPS was evaluated. Notably, Ag-NPS resin displayed the pronounced separation capacities for tacrolimus and its equilibrium adsorption data was well-fitted to the Langmuir isotherm. Moreover, the dynamic adsorption and desorption tests was carried out to obtain the operational parameters for further purification of tacrolimus. Finally, tacrolimus and the two major impurities, ascomycin and dihydrotacrolimus, were separated well in the scale-up purification process. The purity and recovery of tacrolimus was recorded to be 99.12±0.25% and 90.41±2.05%. In conclusion, this method displayed a high potential for separation and purification of tacrolimus and other unsaturated bioactive compounds in high yield from the fermentation broth.