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Eucalyptus roots form symbiotic relationships with arbuscular mycorrhizal (AM) fungi in soil to enhance adaptation in challenging environments. However, the evolution of the AM fungal community along a chronosequence of eucalypt plantations and its relationship with soil properties remain unclear. In this study, we evaluated the tree growth, soil properties, and root AM fungal colonization of Eucalyptus grandis W. Hill ex Maiden plantations at different ages, identified the AM fungal community composition by high-throughput sequencing, and developed a structural equation model among trees, soil, and AM fungi. Key findings include the following: (1) The total phosphorus (P) and total potassium (K) in the soil underwent an initial reduction followed by a rise with different stand ages. (2) The rate of AM colonization decreased first and then increased. (3) The composition of the AM fungal community changed significantly with different stand ages, but there was no significant change in diversity. (4) Paraglomus and Glomus were the dominant genera, accounting for 70.1% and 21.8% of the relative abundance, respectively. (5) The dominant genera were mainly influenced by soil P, the N content, and bulk density, but the main factors were different with stand ages. The results can provide a reference for fertilizer management and microbial formulation manufacture for eucalyptus plantations.
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Leukemic stem cells (LSCs) in chronic myeloid leukemia (CML) contribute to treatment resistance and disease recurrence. Metabolism regulates LSCs, but the mechanisms remain elusive. Here, we show that hypoxia-inducible factor 2α (HIF-2α) is highly expressed in LSCs in mouse and human CML and increases after tyrosine kinase inhibitor (TKI) treatment. Deletion of HIF-2α suppresses disease progression, reduces LSC numbers, and enhances the efficacy of TKI treatment in BCL-ABL-induced CML mice. Mechanistically, HIF-2α deletion reshapes the metabolic profile of LSCs, leading to increased production of reactive oxygen species (ROS) and apoptosis in CML. Moreover, HIF-2α deletion decreases vascular endothelial growth factor (VEGF) expression, thereby suppressing neovascularization in the bone marrow of CML mice. Furthermore, pharmaceutical inhibition of HIF-2α by PT2399 attenuates disease progression and improves the efficacy of TKI treatment in both mouse and human CML. Overall, our findings highlight the role of HIF-2α in controlling the metabolic state and vascular niche remodeling in CML, suggesting it is a potential therapeutic target to enhance TKI therapy.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Leucemia Mielógena Crónica BCR-ABL Positiva , Células Madre Neoplásicas , Inhibidores de Proteínas Quinasas , Microambiente Tumoral , Animales , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/antagonistas & inhibidores , Ratones , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Microambiente Tumoral/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Apoptosis/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Iron and phosphorus are essential nutrients that exist at low concentrations in surface waters and may be co-limiting resources for phytoplankton growth. Here, we show that phosphorus deficiency increases the growth of iron-limited cyanobacteria (Synechocystis sp. PCC 6803) through a PhoB-mediated regulatory network. We find that PhoB, in addition to its well-recognized role in controlling phosphate homeostasis, also regulates key metabolic processes crucial for iron-limited cyanobacteria, including ROS detoxification and iron uptake. Transcript abundances of PhoB-targeted genes are enriched in samples from phosphorus-depleted seawater, and a conserved PhoB-binding site is widely present in the promoters of the target genes, suggesting that the PhoB-mediated regulation may be highly conserved. Our findings provide molecular insights into the responses of cyanobacteria to simultaneous iron/phosphorus nutrient limitation.
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Proteínas Bacterianas , Regulación Bacteriana de la Expresión Génica , Hierro , Fósforo , Synechocystis , Fósforo/metabolismo , Fósforo/deficiencia , Synechocystis/metabolismo , Synechocystis/genética , Hierro/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Regiones Promotoras Genéticas/genética , Agua de Mar/microbiología , Homeostasis , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Leukaemia stem cells (LSCs) in acute myeloid leukaemia present a considerable treatment challenge due to their resistance to chemotherapy and immunosurveillance. The connection between these properties in LSCs remains poorly understood. Here we demonstrate that inhibition of tyrosine phosphatase SHP-1 in LSCs increases their glycolysis and oxidative phosphorylation, enhancing their sensitivity to chemotherapy and vulnerability to immunosurveillance. Mechanistically, SHP-1 inhibition leads to the upregulation of phosphofructokinase platelet (PFKP) through the AKT-ß-catenin pathway. The increase in PFKP elevates energy metabolic activities and, as a consequence, enhances the sensitivity of LSCs to chemotherapeutic agents. Moreover, the upregulation of PFKP promotes MYC degradation and, consequently, reduces the immune evasion abilities of LSCs. Overall, our study demonstrates that targeting SHP-1 disrupts the metabolic balance in LSCs, thereby increasing their vulnerability to chemotherapy and immunosurveillance. This approach offers a promising strategy to overcome LSC resistance in acute myeloid leukaemia.
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Leucemia Mieloide Aguda , Reprogramación Metabólica , Humanos , Monitorización Inmunológica , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Células Madre , Células Madre Neoplásicas/metabolismoRESUMEN
A carboxylesterase fluorescent probe (Probe 1) was developed for determination of carboxylesterase to guide detection of carbamate pesticide. The probe uses benzothiazole as fluorescence group and phenyldimethyl carbamate as recognition group. The solution of the fluorescent probe gradually changes from light blue to dark blue as the concentration of carbamate pesticides increases. The concentration of carbamate pesticides can be quickly calculated according to the colour of the probe solution through Get Color software on a smartphone. It showed that Probe 1 can be used as a rapid detection tool to achieve rapid detection of carbamate pesticides in juice samples without professional personnel and equipment. Furthermore, the probe has been successfully used to detect carbamate pesticides in fruit juice and vegetable juice.
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Carboxilesterasa , Plaguicidas , Colorantes Fluorescentes , Fluorescencia , Plaguicidas/análisis , CarbamatosRESUMEN
Sorafenib, a kinase inhibitor, has shown promising therapeutic efficacy in a subset of patients with acute myeloid leukemia (AML). However, despite its clinical effectiveness, sorafenib resistance is frequently observed in clinical settings, and the mechanisms underlying this resistance as well as effective strategies to overcome it remain unclear. We examined both single-cell and bulk transcription data in sorafenib-resistant and control AML patients and integrated a sorafenib resistance gene signature to predict the sensitivity of AML cells and the clinical outcomes of AML patients undergoing sorafenib therapy. In addition, our drug sensitivity analysis of scRNA-seq data using deconvolution methods showed that venetoclax was effective in targeting sorafenib-resistant AML cells. Mechanistically, sorafenib was found to activate the JAK-STAT3 pathway and upregulate BCL2 expression in sorafenib-resistant AML cells. This upregulation of BCL2 expression rendered the cells vulnerable to the BCL2 inhibitor venetoclax. In conclusion, we developed a platform to predict sorafenib resistance and clinical outcomes in AML patients after therapy. Our findings suggest that the combination of sorafenib and venetoclax could be an effective therapeutic strategy for AML treatment.
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Background: Acute type A aortic dissection (ATAAD) is life-threatening and needs urgent and highly invasive surgery. So far, there is no comprehensive review of the status quo of ATAAD studies. Therefore, this study aimed to quantify and identify the global trends of ATAAD research over the past two decades through bibliometric analysis and to provide reference for clinical practice, research funding allocation, and decision-making. Methods: The original research articles and reviews related to ATAAD research were downloaded from the Web of Science Core Collection on March 19, 2023. CiteSpace (6.2.1) and VOSviewer (1.6.18) were used for bibliometric analysis of the number of publications by each country, institution, and authors and the establishment of knowledge maps. The raw data collected were examined using the Online Analysis Platform of Bibliometric to assess the collaboration of countries in the field. Results: The number of documents on ATAAD research increased continuously. A total of 1,943 publications published from 2002 to 2022 from 66 countries/regions were identified: 637 (32.78%) were conducted in China and 360 (18.53%) in the United States; 152 (cited frequency 941) were conducted by Capital Medical University and 107 (cited frequency 370) by Fujian Medical University. The Journal of Cardiac Surgery was the most frequently published journal (143 publications, cited frequency 695). The highest citation and co-cited journal was the Annals of Thoracic Surgery (cited frequency 3,888, co-cited frequency 6,224). We identiï¬ed 8,050 authors among which Lizhong Sun (61 publications, cited frequency 721) had the largest number of publications, and Nienaber Christoph A (cited frequency 1,536, co-cited frequency 392) was co-cited most often. Meanwhile, the most common keywords were acute type A aortic dissection (occurrences, 1,211), surgery (occurrences, 657), repair (occurrences, 404), and management (occurrences, 386). The earliest and latest used keywords were "axillary artery" (average publication year: 2011.23) and "inflammation" (average publication year: 2019.09), respectively. The keyword "surgical treatment" (strength 12.31) and the co-cited reference "Evangelista A, 2018, Circulation" (strength 28.55) had the highest citation bursts. The keywords "impact" and "acute kidney injury" remained high citation bursts. The co-cited references with the largest and smallest size clusters were "cerebral protection" (#0, size = 126) and "pregnancy" (#12, size = 11). The reference "Hagan PG, 2000, JAMA" (cited frequency, 350) had the highest co-citations. Conclusions: The bibliometric and visualized analysis generated objective evidence for a comprehensive understanding and evaluation of ATAAD research.
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BACKGROUND: A growing body of research has revealed the connection of metabolism reprogramming and tumor progression, yet how metabolism reprogramming affects inter-patient heterogeneity and prognosis in head and neck squamous cell carcinoma (HNSCC) still requires further explorations. METHODS: A cellular hierarchy framework based on metabolic properties discrepancy, METArisk, was introduced to re-analyze the cellular composition from bulk transcriptomes of 486 patients through deconvolution utilizing single-cell reference profiles from 25 primary and 8 metastatic HNSCC sample integration of previous studies. Machine learning methods were used to identify the correlations between metabolism-related biomarkers and prognosis. The functions of the genes screened out in tumor progression, metastasis and chemotherapy resistance were validated in vitro by cellular functional experiments and in vivo by xenograft tumor mouse model. RESULTS: Incorporating the cellular hierarchy composition and clinical properties, the METArisk phenotype divided multi-patient cohort into two classes, wherein poor prognosis of METArisk-high subgroup was associated with a particular cluster of malignant cells with significant activity of metabolism reprogramming enriched in metastatic single-cell samples. Subsequent analysis targeted for phenotype differences between the METArisk subgroups identified PYGL as a key metabolism-related biomarker that enhances malignancy and chemotherapy resistance by GSH/ROS/p53 pathway, leading to poor prognosis of HNSCC. CONCLUSION: PYGL was identified as a metabolism-related oncogenic biomarker that promotes HNSCC progression, metastasis and chemotherapy resistance though GSH/ROS/p53 pathway. Our study revealed the cellular hierarchy composition of HNSCC from the cell metabolism reprogramming perspective and may provide new inspirations and therapeutic targets for HNSCC in the future.
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Neoplasias de Cabeza y Cuello , Humanos , Animales , Ratones , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Especies Reactivas de Oxígeno , Proteína p53 Supresora de Tumor/genética , Pronóstico , Regulación Neoplásica de la Expresión GénicaRESUMEN
Background: Rheumatoid arthritis (RA) joint inflammation severely affects joint function and quality of life in patients and leads to joint deformities and limb disability. The non-steroidal anti-inflammatory drugs used in the treatment of RA do not fully control the progression of joint inflammation and bone destruction and have notable adverse reactions. Traditional Chinese medicine formula JuanBiQiangGu Granules (JBQG) are commonly used for the treatment of RA inflammation and delay of bone destruction, but has not been evaluated through high-quality clinical studies. There is a pressing need for well-designed, randomized, parallel, controlled clinical studies to evaluate the exact effect of JBQG on RA joint inflammation and improvement of patient quality of life. Methods: This is a randomized, parallel, controlled clinical study in which 144 patients with rheumatoid arthritis who met the inclusion criteria were randomly assigned to 2 groups in a 1:1 ratio. The JBQG group received methotrexate 7.5 mg qw and JBQG granules 8 mg tid, while the MTX group received methotrexate 7.5 mg qw. The endpoint was 12 weeks after treatment. Relevant indices at baseline, 4 weeks, 8 weeks, and 12 weeks after treatment were observed and recorded, and DAS28-ESR, HAQ-DI, and Sharp scores were recorded for each patient. Blood samples were collected to test for CRP, ESR, TNF-α, IL-1ß, IL-6, IL-17, and INF-γ, and adverse reactions and liver and kidney function (AST, ALT, Cr, BUN) were recorded for safety assessment. After 12 weeks of treatment, the effect of JBQG granules on disease activity, improvement in bone damage, and patient quality of life scores and safety in RA patients were evaluated. Results: A total of 144 subjects completed treatment (71 in the JBQG group and 73 in the MTX group) and were included in the analysis. At baseline, there were no significant differences between the groups in terms of the observed indicators (p > 0.05). After treatment, 76.06% of patients in the JBQG group had DAS28-ESR levels below or equal to Low, including 45.07% in Remission and 5.63% in High, compared to 53.1% in the MTX group below or equal to Low, 12.33% in Remission, and 17.81% in High. CRP was significantly reduced (8.54 ± 5.87 vs. 11.86 ± 7.92, p < 0.05, p = 0.005), ESR was significantly reduced (15.1 ± 6.11 vs. 21.96 ± 9.19, p < 0.0001), TNF-α was significantly reduced (1.44 ± 0.83 vs. 1.85 ± 1.07, p < 0.05, p = 0.011), IL-17 was significantly reduced (0.53 ± 0.33 vs. 0.71 ± 0.38, p < 0.05, p = 0.004), and INF-γ was significantly reduced (3.2 ± 1.51 vs. 3.89 ± 1.77, p < 0.05, p = 0.014). The median (IQR) OPG in the JBQG group was 2.54 (2.21-3.01), significantly higher than in the MTX group 2.06 (1.81-2.32), p < 0.0001), and the median (IQR) ß-CTX in the JBQG group was 0.4 (0.32-0.43), significantly lower than in the MTX group 0.55 (0.47-0.67), p < 0.0001). The median (IQR) VSA scores were 2 (1-3), a decrease from 3 (2-4) in the MTX group (p < 0.0001). The median (IQR) Sharp scores were 1 (1-2), a decrease from 2 (1-2) in the MTX group, but the difference was not statistically significant (p > 0.05, p = 0.28). The median (IQR) HAQ-DI scores were 11 (8-16), significantly lower than in the MTX group 26 (16-30) (p < 0.0001). The median (IQR) AST in the JBQG group was 16 (12-20), with a significant difference compared to the MTX group 19 (13-25) (p < 0.01, p = 0.004); the median (IQR) ALT in the JBQG group was 14 (10-18), with a significant difference compared to the MTX group 16 (11-22.5) (p < 0.05, p = 0.015). There were no statistically significant differences in Cr or BUN (p > 0.05). Conclusion: JuanBiQiangGu Granules can be used to treat patients with rheumatoid arthritis, alleviate joint inflammation, reduce the incidence of adverse reactions to methotrexate, and has good safety. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html; identifier: ChiCTR2100046373.
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Objective: This study evaluated the reno-protective effects of quercetin in animal models of acute kidney injury (AKI). Methods: We conducted a systematic search of literature published before April 2023 in PubMed, Web of Science, and EMBASE databases. Methodological quality was assessed by SYRCLE's RoB tool. Funnel plot, Egger's test, and Begg's test were used to determine publication bias. Results: A total of 19 studies with 288 animals were included in this meta-analysis. The methodology quality scores of the included studies ranged from 4 to 7. The results indicated that quercetin reduced blood urea nitrogen (SMD = -4.78; 95% CI: 6.45, -3.12; p < 0.01; I2 = 84%) and serum creatinine (SMD: 2.73, 95% CI: 3.66, -1.80; p < 0.01; I2 = 80%) in AKI models. The result of sensitivity analysis was stable, while the results of funnel plot indicated asymmetric. In addition, we further analyzed inflammatory cytokines, oxidative stress levels, and kidney injury scores, and found that quercetin treatment had antioxidant and anti-inflammatory effects and improved kidney injury scores in animal models of AKI. Conclusion: Quercetin exhibited a promising reno-protective effect in AKI animal models. Systematic Review Registration: PROSPERO (CRD42023433333).
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A multifunctional design based on vanadium dioxide (VO2) metamaterial structure is proposed. Broadband absorption, linear-to-linear (LTL) polarization conversion, linear-to-circular (LTC) polarization conversion, and total reflection can be achieved based on the insulator-to-metal transition (IMT) of VO2. When the VO2 is in the metallic state, the multifunctional structure can be used as a broadband absorber. The results show that the absorption rate exceeds 90% in the frequency band of 2.17 - 4.94 THz, and the bandwidth ratio is 77.8%. When VO2 is in the insulator state, for the incident terahertz waves with a polarization angle of 45°, the structure works as a polarization converter. In this case, LTC polarization conversion can be obtained in the frequency band of 0.1 - 3.5 THz, and LTL polarization conversion also can be obtained in the frequency band of 3.5 - 6 THz, especially in the 3.755 - 4.856 THz band that the polarization conversion rate is over 90%. For the incident terahertz waves with a polarization angle of 0°, the metamaterial structure can be used as a total reflector. Additionally, impacts of geometrical parameters, incidence angle and polarization angle on the operating characteristics have also been investigated. The designed switchable multifunctional metasurfaces are promising for a wide range of applications in advanced terahertz research and smart applications.
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[This retracts the article DOI: 10.3892/ol.2018.8109.].
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The occurrence of ectopic intrathyroidal parathyroid adenoma (EPTA) is very rare, which causes some difficulties in diagnosis and complicates treatment. In addition, the occurrence of EPTA with nodular goiter (NG) is rare, which makes diagnosis difficult and requires the assistance of clinical evidence, imaging data, and cytological examination results. Therefore, we present a patient with a final diagnosis of ETPA with NG.
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In this paper, a novel, to the best of our knowledge, polymer-based negative curvature ring-core fiber (NC-RCF) is proposed and investigated. The hollow-core NC-RCF is composed of TOPAS as background material. The inner and outer negative curvature structure layers are connected to the annular area, and the orbital angular momentum (OAM) modes can propagate in the annular core. In the frequency region of 1.0-1.5 THz, the designed NC-RCF can stably transmit 82 OAM modes. Investigation results indicate that the effective refractive index differences between the corresponding HE and EH modes are above 10-4. The confinement losses of EH or HE modes are smaller than 10-8 d B/m, and the dispersion variations are lower than 0.31 ps/THz/cm. Effective mode areas are larger than 5.14m m 2. Additionally, the highest mode purity of all vector modes is 99.78%. In addition, modal birefringence, also known as the walk-off length, has also been discussed. All these operation performances indicate that the designed NC-RCF make contributions to the optical communication systems.
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Bilirubin encephalopathy (BE) is a neurological syndrome in newborns, mainly caused by neuronal injury due to excessive oxidative stress produced by unconjugated bilirubin (UCB). Neuroglobin (NGB) can protect the brain by removing oxidative stress species, but its expression and significance in BE are not clear. To address this question, the neonatal BE model was established by injecting UCB into the cerebellomedullary cistern of 7-day-old SD rats. Rats were divided into a sham and BE 6 hr group, BE 12 hr group, BE 24 hr group, and BE 7 d group according to UCB action times. Hematoxylin/eosin and Nissl staining, and electron microscopy were employed to observe the pathological and ultrastructural changes of nerve cells in each group. Immunofluorescence staining was used to detect NGB expression sites and cell types. Western blotting and quantitative PCR served to detect NGB expression and test the mitochondrial apoptosis signal pathway. The results confirm that UCB can lead to pathological damage and ultrastructural changes in rats' temporal cortex, increasing the expression of apoptosis-related proteins Bax, Bcl-2, Cyt c, Caspase-3, and neuronal NGB. UCB promotes NGB expression with an increase in action time and reach a peak at 12 hr. In summary, brain damage induced by UCB will cause an increase in NGB expression, the increasing NGB can inhibit neuron apoptosis in early BE phases. Therefore, promoting the expression of endogenous NGB, to act as a neuroprotective agent may be a potential treatment strategy for BE.
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Globinas , Kernicterus , Animales , Globinas/genética , Globinas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuroglobina , Ratas , Ratas Sprague-Dawley , Lóbulo Temporal/metabolismoRESUMEN
Iron is an essential micronutrient for the ecologically important photoautotrophic cyanobacteria which are found across diverse aquatic environments. Low concentrations and poor bioavailability of certain iron species exert a strong control on cyanobacterial growth, affecting ecosystem structure and biogeochemical cycling. Here, we review the iron-acquisition pathways cyanobacteria utilize for overcoming these challenges. As the molecular details of cyanobacterial iron transport are being uncovered, an overall scheme of how cyanobacteria handle and exploit this scarce and redox-active micronutrient is emerging. Importantly, the range of biological solutions used by cyanobacteria to increase iron fluxes goes beyond transport and includes behavioral traits of colonial cyanobacteria and intricate cyanobacteria-bacteria interactions.
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Cianobacterias , Ecosistema , Cianobacterias/metabolismo , Hierro/metabolismo , Oxidación-ReducciónRESUMEN
OBJECTIVE: To analyze the clinicobiological heterogeneity of NPM1 mutated (NPM1mut) acute myeloid leukemia (AML) detected by next generation sequencing (NGS) and their coexistence and mutual exclusivity relationship in the AML subtype. METHODS: The NGS data based on 112 genes related to blood disease in 238 newly diagnosed patients with NPM1mut were collected. The χ2 test and non-parametric test were used to analyze the distribution correlation between the genes in the mutational spectrum. RESULTS: Among all the patients, at least one co-mutation was detected out. The median number per case of the mutated genes, including NPM1mut was 4.5 (range 2ï¼14), among them, there were 5.0 (range 2ï¼10) for NPM1mut/FLT3-ITD+ and 4.0 (range 2ï¼14) for NPM1mut/FLT3-ITD- cases, but it was no significant difference between the two groups (P=0.378). A total of 240 NPM1 mutational events were detected out in entire 238 NPM1mut patients, of which 10 (4.2%) were missense mutations, and were all found in NPM1mut/FLT3-ITD- patients. Most (9/10, 90%) of these NPM1 missense mutations were accompanied by AML subtype-defining cytogenetic or molecular abnormalities, of which 7 patients were in low risk or 2 in high risk. The most common NPM1mut coexisting mutations were DNMT3A (104, 43.7%), followed were FLT3-ITD (95, 39.9%) and FAT1 (57, 23.9%), FLT3-ITD and DNMT3A showed significant coexistence (P=0.005). FLT3-ITD showed significantly reciprocal exclusivity with FLT3-nonITD (P<0.001), NRAS (P<0.001), PTPN11 (P=0.017) and IDH1 (P=0.005), and showed an exclusivity inclination with KRAS (P=0.073). In addition, FLT3-nonITD along with KRAS (P=0.035), NRAS along with KRAS (P=0.008) and PTPN11 (P=0.039) coexisted significantly. CONCLUSION: Prognoses of AML involving less common NPM1 missense mutations should be stated on a case by case basis. The mutational landscape and co-occurrence and mutual exclusivity correlations of NPM1mut AML provide a mechanism explaining biological diversity and clinical heterogeneity in this AML subset.
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Leucemia Mieloide Aguda , Proteínas Nucleares , Secuencia de Bases , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leucemia Mieloide Aguda/genética , Mutación , Proteínas Nucleares/genéticaRESUMEN
Nutritional starvation (NST) is the basis of tumor anti-angiogenesis and metabolic therapy strategy. Silencing Akt1 inhibits prostate cancer (PCa) cells growing; slow-growing cells tend to consume less nutrition. It is suggested that Akt1-silenced cancer cells will have a more substantial tolerance to NST. Clarify this critical question is vital for tumor treatment strategies based on Akt1 and NST. The Akt1 gene of PC3 and DU145 cells was silenced by lent-virus. NST model was established by serum stripping. Cell viability was detected by MTT assay and cell counting method. Apoptosis was detected by TUNEL and flow cytometry, and cell invasion was determined by transwells and ECIS. The markers of epithelial-mesenchymal transition (EMT) were detected by western blotting. PCa lung metastasis model was established by tail vein injection and quantified by Indian ink and GFP fluorescence. Silencing Akt1 slowed down the decrease of cell number and increase of apoptosis caused by NST. Silencing Akt1 with NST exposure in PCa cells could down-regulate epithelial markers (E-cadherin, claudin-5, and ZO-1) and up-regulate mesenchymal markers N-cadherin and EMT regulators Snail. Although silencing Akt1 enhanced the invasion of PCa cells induced by NST in vitro, silencing Akt1 inhibited the PCa lung metastasis induced by NST in vivo. Silencing Akt1 gene enhances the resistance of PCa cells to NST. The invasion results in vitro were inconsistent with those metastases in vivo, which may be related to a combination of NST with silencing Akt1 to maintain the mesenchymal state of PCa cells through EMT.
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Transición Epitelial-Mesenquimal/genética , Neoplasias Pulmonares , Neoplasias de la Próstata , Proteínas Proto-Oncogénicas c-akt/genética , Estrés Fisiológico/genética , Animales , Apoptosis/genética , Línea Celular Tumoral , Silenciador del Gen , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Desnudos , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patologíaRESUMEN
The goal of the present study was to disclose the interactions between chitosan-type chiral selectors (CSs) and chiral analytes during enantioseparation. Hence, six chitosan 3,6-bis(phenylcarbamate)-2-(cyclohexylmethylurea)s were synthesized and characterized. These chitosan derivatives were employed as CSs with which the corresponding coated-type chiral stationary phases (CSPs) were prepared. According to the nature and position of the substituents on the phenyl group, the CSs and CSPs were divided into three sets. The counterparts of the three sets were 3,5-diMe versus 3,5-diCl, 4-Me versus 4-Cl and 3-Me versus 3-Cl. The enantioseparation capability of the CSPs was evaluated with high-performance liquid chromatography. The CSPs demonstrated a good enantioseparation capability to the tested chiral analytes. In enantioselectivity, the CSs with 3,5-diCl and with 4-Me roughly were better than the counterparts with 3,5-diMe and with 4-Cl respectively. The CS with 3-Me enantiomerically recognized more analytes than the one with 3-Cl, but showed lower separation factors in more enantioseparations. The acidity of the amide hydrogen in the phenylcarbamates was investigated with density functional theory calculations and 1H NMR measurements. The trend of the acidity variation with different substituents on the phenyl group was confirmed by the retention factors of acetone on the CSPs. Compared the retention factors of analytes on every set of the counterparts, the formation of hydrogen bond (HB) in enantioseparation could be outlined as follows: when the CSs interacted with chiral analytes without reactive hydrogen but with lone paired electrons, the carbamate NâHs in the CSs were HB donors and the analytes were HB acceptors; if the CSs interacted with analytes with a reactive hydrogen, the role of the CSs in HB formation was related to the acidity of the reactive hydrogen; the patterns of HB formation between the CSs and analytes were also impacted by compositions of mobile phases, in addition to the nature, number and position of substituents on the phenyl group. Based on the discussion, chiral recognition mechanism could be understood in more detail. Besides, the strategy to improve enantioseparation capability of a CSP by introducing a substituent onto phenyl group was clarified and further comprehended.