Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 250
Filtrar
1.
Entropy (Basel) ; 24(9)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36141067

RESUMO

Due to the complicated engineering operation of the check valve in a high-pressure diaphragm pump, its vibration signal tends to show non-stationary and non-linear characteristics. These leads to difficulty extracting fault features and, hence, a low accuracy for fault diagnosis. It is difficult to extract fault features accurately and reliably using the traditional MPE method, and the ELM model has a low accuracy rate in fault classification. Multi-scale weighted permutation entropy (MWPE) is based on extracting multi-scale fault features and arrangement pattern features, and due to the combination of extracting a sequence of amplitude features, fault features are significantly enhanced, which overcomes the deficiency of the single-scale permutation entropy characterizing the complexity of vibration signals. It establishes the check valve fault diagnosis model from the twin extreme learning machine (TELM). The TELM fault diagnosis model established, based on MWPE, aims to find a pair of non-parallel classification hyperplanes in the equipment state space to improve the model's applicability. Experiments show that the proposed method effectively extracts the characteristics of the vibration signal, and the fault diagnosis model effectively identifies the fault state of the check valve with an accuracy rate of 97.222%.

2.
Br J Cancer ; 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088509

RESUMO

BACKGROUND: The E3 ubiquitin ligase HECTD3 is a homologue of the E6-related protein carboxyl terminus, which plays a crucial role in biological processes and tumourigenesis. However, the functional characterisation of HECTD3 in glioblastoma is still elusive. METHODS: Determination of the functional role of HECTD3 in glioblastoma was made by a combination of HECTD3 molecular pattern analysis from human glioblastoma databases and subcutaneous and in situ injections of tumours in mice models. RESULTS: This study reports that the DOC domain of HECTD3 interacts with the DNA binding domain of PARP1, and HECTD3 mediated the K63-linked polyubiquitination of PARP1 and stabilised the latter expression. Moreover, the Cysteine (Cys) 823 (ubiquitin-binding site) mutation of HECTD3 significantly reduced PARP1 polyubiquitination and HECTD3 was involved in the recruitment of ubiquitin-related molecules to PARP1 ubiquitin-binding sites (Lysines 209 and 221, respectively). Lastly, activation of EGFR-mediated signalling pathways by HECTD3 regulates PARP1 polyubiquitination. CONCLUSION: Our results unveil the potential role of HECTD3 in glioblastoma and strongly preconise further investigation and consider HECTD3 as a promising therapeutic marker for glioblastoma treatment.

3.
Oncogene ; 41(37): 4295-4306, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35978151

RESUMO

SMARCE1 gene, encoding a core subunit of SWI/SNF chromatin remodeling complex, is situated on chromosome 17q21-ter region that is frequently gained in neuroblastoma. However, its role in the tumorigenesis remains unknown. Here, we showed that high expression of SMARCE1 was associated with poor prognosis of patients with neuroblastoma, especially those with MYCN amplification. Knockdown of SMARCE1 reduced proliferation, colony formation, and tumorigenicity of neuroblastoma cells. Mechanistically, SMARCE1 directly interacted with MYCN, which was necessary for MYCN-mediated transcriptional activation of downstream target genes including PLK1, ODC1, and E2F2. Overexpression of PLK1, ODC1 or E2F2 significantly reversed the inhibiting effect of SMARCE1 knockdown on the proliferation, colony formation, and tumorigenicity of MYCN-amplified neuroblastoma cells. Moreover, we revealed that MYCN directly regulated SMARCE1 transcription through binding to a non-canonical E-box of SMARCE1 promoter, thus enhancing SMARCE1-MYCN cooperativity. These findings establish SMARCE1 is a critical oncogenic factor in neuroblastoma and provide a new potential target for treatment of neuroblastoma with 17q21-ter gain and MYCN amplification.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neuroblastoma , Carcinogênese/genética , Linhagem Celular Tumoral , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/genética , Humanos , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Neuroblastoma/genética , Neuroblastoma/metabolismo , Ativação Transcricional/genética
4.
Front Plant Sci ; 13: 946827, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968130

RESUMO

Erigeron breviscapus, a traditional Chinese medicinal plant, is enriched in flavonoids that are beneficial to human health. While we know that R2R3-MYB transcription factors (TFs) are crucial to flavonoid pathway, the transcriptional regulation of flavonoid biosynthesis in E. breviscapus has not been fully elucidated. Here, EbMYBP1, a R2R3-MYB transcription factor, was uncovered as a regulator involved in the regulation of flavonoid accumulation. Transcriptome and metabolome analysis revealed that a large group of genes related to flavonoid biosynthesis were significantly changed, accompanied by significantly increased concentrations of the flavonoid in EbMYBP1-OE transgenic tobacco compared with the wild-type (WT). In vitro and in vivo investigations showed that EbMYBP1 participated in flavonoid biosynthesis, acting as a nucleus-localized transcriptional activator and activating the transcription of flavonoid-associated genes like FLS, F3H, CHS, and CHI by directly binding to their promoters. Collectively, these new findings are advancing our understanding of the transcriptional regulation that modulates the flavonoid biosynthesis.

5.
Membranes (Basel) ; 12(8)2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-36005670

RESUMO

An integrated membrane bioreactor (MBR) with synthetic RO membrane cleaning wastewater from a thermal power plant was used to study the long-term operating characteristics, membrane fouling, and cleaning of membrane fouling. The results show that the MBR had a great removal effect on mainly an organic pollutant (citric acid) with an average of 98.4% rejection, and the concentration of organics in the effluent also achieved "Discharge standard of pollutants for municipal wastewater treatment plant" (GB12/599-2015). The optimal operating conditions were as follows: the membrane flux was 8 L/(m2·h); the hydraulic retention time (HRT) was 4 h; the sludge retention time (SRT) was 15 d, and the pH value was 6~7. A membrane fouling analysis showed that the resistance of the cake layer and the concentration polarization were the main components of membrane fouling. When the specific flux (SF) decreased to 10 L/(h·m2 mH2O), the membrane module was cleaned by tap water and then soaked in 0.05 wt% hydrochloric acid (HCl) and 3000 mg/L sodium hypochlorite (NaOCl) for 1 h and 3 h, respectively. Finally, the membrane flux could be recovered to 84.9% compared to the new membrane.

6.
Aging (Albany NY) ; 14(14): 5749-5767, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35832033

RESUMO

The relationship between red blood cell distribution width (RDW) in peripheral thrombolysis period and prognosis is not fully clarified in those who underwent intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). Our study aimed to clarify this issue. A retrospective analysis of about 510 consecutive thrombolysis cases for AIS from January 2015 to March 2019 in a single-center database was done and followed-up for 3 months. We used univariate and multivariable models to evaluate the relationship between RDW levels at various time-points after IVT and the occurrence risk of hemorrhagic transformation (HT) and recurrent stroke, and used COX regression to assess the hazard ratios of outcomes with RDW levels. Elevated risk of HT was found in higher tertiles of RDW (OR = 10.282, 95% confidence interval (CI) 2.841-39.209, P < 0.001 in Tp tertile G3; OR = 5.650, 95% CI 1.992-16.025, P = 0.001 in T24 tertile G3; OR = 4.308, 95% CI 1.480-12.542, P = 0.007 in T48 tertile G3 and OR = 6.384, 95% CI 2.201-18.515, P = 0.001 in T72 tertile G3, respectively). Occurrence of recurrent stroke was highest in the RDW tertile G3 (HR = 4.580, 95% CI 2.123-9.883, P < 0.001 in Tp tertile G3; HR = 5.731, 95% CI 2.498-13.151, P = 0.001 in T24 tertile G3; HR = 3.019, 95% CI 1.969-4.059, P = 0.031 in T48 tertile G3; HR = 3.318, 95% CI 1.598-6.890, P = 0.001 in T72 tertile G3, respectively). Mean RDW levels ≥13.60 among AIS patients undergoing thrombolysis was associated with higher risk of HT and recurrent stroke.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Eritrócitos , Humanos , AVC Isquêmico/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Terapia Trombolítica
8.
Front Hum Neurosci ; 16: 894911, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814947

RESUMO

Background: Methamphetamine addicts can experience severe emotional processing disorders, with abnormal responses to emotional and drug-related stimuli. These aberrant behaviors are one of the key factors leading to relapse. Nevertheless, the characteristics of addicts' responses to drug-related stimuli and their responses to emotional stimuli remain controversial. Methods: 52 methamphetamine addicts from China passively viewed three different categories of images: Drug-related; positive emotional; and negative emotional. In the first task, participants completed a 9-point Self-Assessment Manikin (SAM) scale, rating the valence of each image. In the second, they performed a cued-action task while electroencephalography (EEG) data were recorded. Result: Drug-related images were rated negatively, with an average rating of 3.57. However, reaction times to drug-related stimuli were significantly faster than for negative stimuli (p = 0.030), and were indistinguishable from positive stimuli (p > 0.99). Similarly, EPN amplitudes evoked by drug-related images were significantly larger than those evoked by negative stimuli (p < 0.001), but no different than positive stimuli (p > 0.99). LPP amplitudes evoked by drug-related stimuli were significantly smaller than those evoked by negative (p < 0.001) and positive stimuli (p = 0.004). Conclusion: Despite negative self-assessments of drug-related imagery, MA-addicts reaction times were no slower than positive reactions. Similarly, drug-related and positive imagery EPN amplitudes were indistinguishable. Together, these results suggest increased attentional resources were allocated to the processing of drug-related stimuli and the pathways responsible partially overlap with the those recruited in processing positive emotional imagery in addicts. Moreover, in the late stage of visual processing, MA-addicts showed reduced brain activity in response to drug-related stimuli, suggesting reverse inhibition in response preparation and emotional appraisal. These findings may provide a reference for clinicians treating drug-taking behavior and for the development of new models of rehabilitation therapy.

9.
Arch Microbiol ; 204(8): 500, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35851419

RESUMO

Arthrobotrys oligospora is a model nematode-trapping fungus that has been extensively investigated to understand the interactions between fungi and nematodes. Nematode capture by A. oligospora is a complex process in which recognition of nematodes is generally believed to be mediated by lectins from the fungi. Lectins are a group of carbohydrate-binding proteins that widely exist in microorganisms and contain specific glycosylation recognition domains. In this work, we report the effect of a putative WSC domain-containing protein encoding gene AOL_s00043g401 (g401) on the growth and nematode-trapping of A. oligospora. The g401 gene was knocked out using the homologous recombination approach, and the △g401 mutant strain was then evaluated for its growth rate, conidial yield and germination rate, adaptation to environmental stresses, and nematocidal activity. Interestingly, the deletion of the putative lectin gene g401 had no significant effect on saprophytic growth, conidial yield and germination rate, responses to high salt, surfactant, and strong oxidative environments, as well as nematode-trapping efficiency of A. oligospora. We speculate that this phenomenon might have been caused by an intrinsic genetic compensation of the g401 in this fungus. For instance, more copies of WSC domain encoding genes or PQQ-DH domain encoding genes were found in the genome of A. oligospora. These findings provide further experimental evidence on the effect of lectin-related functional proteins in A. oligospora on nematode capture and will help further analyze their potential roles in the biological control of nematodes in the future.


Assuntos
Ascomicetos , Nematoides , Animais , Ascomicetos/fisiologia , Lectinas , Nematoides/genética , Esporos Fúngicos/genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-35876712

RESUMO

Directly and quickly detecting toxic gases in the air is urgently needed in industrial production and our daily life. However, the poor gas selectivity and low sensitivity under ambient conditions limit the development of gas sensors. In this work, we demonstrate that the penta-BeP2 monolayer is an excellent toxic gas sensor by using first-principles calculations. The calculated results show that the semiconducting penta-BeP2 monolayer can chemisorb toxic gas molecules (including CO, NH3, NO, and NO2) with distinct charge transfer (-0.182 to 1.129 e) but negligibly interact with ambient gas molecules (including H2, N2, H2O, O2, and CO2), indicating high gas selectivity for primary environmental gases. The calculated I-V curves show that the penta-BeP2 monolayer exhibits a fast response with toxic gas molecules. Upon interaction with CO, NH3, NO, and NO2 molecules at a bias voltage of 0.7 V, the currents are 10.23, 14.48, 32.10, and 129.90 times that of the pristine penta-BeP2 monolayer, respectively, which induces high sensitivity values of 9.23, 13.48, 31.10, and 128.90, respectively. Moreover, the moderate adsorption energies of all toxic gas molecules guarantee that the penta-BeP2 monolayer possesses good reversibility at room temperature with a short recovery time. Herein, all of our results indicate that the penta-BeP2 monolayer could be a superior candidate for sensing toxic gases with high selectivity, sensitivity, and reversibility.

11.
J Environ Manage ; 317: 115474, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35751273

RESUMO

Nitrogen loss during composting is closely related to NH4+-N conversion, and ammonia-oxidizing bacteria (AOB) are important microorganisms that promote NH4+-N conversion. Since the biological activity of conventional AOB agents used for compost inoculation declines rapidly during the thermophilic phase of composting, new compound inoculants should be developed that are active during that phase. In the current study, the effects of inoculating cattle manure compost with newly isolated AOB (5%, v/w) [thermotolerant AOB X-2 strain (T-AOB-2), mesophilic AOB X-4 strain (M-AOB-4), and AOB X-2 combined with AOB X-4 (MT-AOB-2-4)] on the conversion of nitrogen, compost maturity, and the resident microbial community were studied. During 35 days of composting, compared with the control, AOB inoculation reduced NH3 emissions by 29.98-46.94%, accelerated the conversion of NH4+-N to NO2--N, increased seed germination values by 13.00-25.90%, and increased the abundance of the microbial community at the thermophilic phase (16.38-68.81%). Network analysis revealed that Bacillaceae play a crucial role in the composting process, with the correlation coefficients: 0.83 (p < 0.05) with NH3, 0.64 (p < 0.05) with NH4+-N, and 0.81 (p < 0.05) with NO2--N. In addition, inoculation with MT-AOB-2-4 notably increased the total nitrogen content of compost, prolonged the sanitation stage, and promoted compost maturity. Hence, MT-AOB-2-4 may be used to increase the microbial community abundance and improve the efficiency of cattle manure composting.


Assuntos
Betaproteobacteria , Compostagem , Microbiota , Amônia , Animais , Bactérias , Bovinos , Esterco/microbiologia , Nitrogênio , Dióxido de Nitrogênio , Oxirredução , Solo
12.
Synth Syst Biotechnol ; 7(3): 958-964, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35756963

RESUMO

Scutellarin related drugs have superior therapeutic effects on cerebrovascular and cardiovascular diseases. Here, an optimal biosynthetic pathway for scutellarin was constructed in Yarrowia lipolytica platform due to its excellent metabolic potential. By integrating multi-copies of core genes from different species, the production of scutellarin was increased from 15.11 mg/L to 94.79 mg/L and the ratio of scutellarin to the main by-product was improved about 110-fold in flask condition. Finally, the production of scutellarin was improved 23-fold and reached to 346 mg/L in fed-batch bioreactor, which was the highest reported titer for de novo production of scutellarin in microbes. Our results represent a solid basis for further production of natural products on unconventional yeasts and have a potential of industrial implementation.

13.
Biochem Biophys Res Commun ; 614: 34-40, 2022 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-35567942

RESUMO

5-Fluorouracil (5-FU) is a chemotherapy drug used to treat tumors. Previous studies have shown that Akkermansia muciniphila (A. muciniphila) and its outer membrane protein, Amuc_1100, alleviate dextran sodium sulfate (DSS)-induced colitis in mice. We investigated the effects of both A. muciniphila and Amuc_1100 on 5-FU-induced intestinal mucosal damage in mice. C57BL/6 mice were gavaged with A. muciniphila or Amuc_1100 daily before, during, and after 5-FU injection for a total of 14 days. By evaluating diarrheal toxicity scores, body weight changes, colonic anatomy images, and histopathology of intestinal injury in these mice, we found that A. muciniphila and Amuc_1100 alleviated 5-FU-induced intestinal mucositis. Quantitative polymerase chain reaction assays of intestinal cytokine mRNA levels demonstrated that both A. muciniphila and Amuc_1100 attenuated the upregulation of intestinal Tumor Necrosis Factor-α (TNF-α) and interleukin-6 (IL-6) induced by 5-FU treatment. In addition, they both reduced 5-FU-induced the NLR family pyrin domain containing 3 (NLRP3) inflammatory vesicle activation. Furthermore, by monitoring the mRNA expression of tight junction proteins in the intestine, we found that A. muciniphila and Amuc_1100 were capable of restoring the damaged intestinal barrier. Notably, A. muciniphila and Amuc_1100 also played a role in altering the structure of the intestinal microbial community. The present study revealed the protective role of both A. muciniphila and Amuc_1100 in the intestinal mucositis caused by 5-FU, providing new insights into treatment options.


Assuntos
Mucosite , Akkermansia , Animais , Fluoruracila/efeitos adversos , Mucosa Intestinal , Intestinos , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , RNA Mensageiro , Verrucomicrobia
14.
Appl Bionics Biomech ; 2022: 5721630, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35465183

RESUMO

Objective: Endometrial carcinoma (EC) ranks first in the incidence of female genital malignancies in developed countries. SPOP (speckle-type POZ protein) has changed in EC with a statistically high frequency. This research may play a crucial role in the initiation and progression of EC, ultimately leading to fresh therapeutic targets. Explore the expression of SPOP in EC; observe its effect on the proliferation, invasion, and migration of EC cells after upregulating the expression of SPOP through RNA activation. Methods: The expression levels of SPOP protein in 150 EC tissues and 45 normal endometrial tissues were detected by immunohistochemistry and Western blotting. Analyze the relationship between SPOP expression and clinicopathological characteristics. The differences of the proliferation, migration, and invasion abilities between before and after transfection were analyzed using CCK-8 and Transwell assays. Results: The results of immunohistochemistry and Western blotting showed the expression level of SPOP in EC tissue significantly reduced or even missed compared with normal endometrial tissue. The results of CCK-8 showed that the growth of EC significantly slowed down after the upregulating of SPOP expression. The results of the Transwell assay showed the migration and invasion abilities of EC cells were weakened after the level of SPOP was upregulated. Conclusions: The expression level of SPOP in EC tissues is lower and related to the clinicopathological features compared with normal endometrial tissues. After upregulating the SPOP expression by RNA activation in EC cell lines, the abilities of proliferation, migration, and invasion of cells were significantly inhibited.

15.
Small ; 18(18): e2200911, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35363427

RESUMO

Single atom sites (SAS) of FeN4 are clarified as one of the most active components for the oxygen reduction reaction (ORR). Effective strategies by engineering the local coordination environment and site density of FeN4 sites are crucial to further enhance the electrocatalytic ORR performance. Herein, the integration of a second metal of Mn with Fe to construct Fe&Mn/N-C catalysts with enhanced density of FeN4 active sites and modulated electronic structure is reported. The formation of MnN4 centers modulates the local environment of FeN4 sites and reserves more FeN4 embedded in carbon substrate by forming the possible FeN4 -O-MnN4 configurations. Density functional theory calculations demonstrate that the overall energy barrier of ORR is decreased over the FeN4 -O-MnN4 moieties. Therefore, the Fe&Mn/N-C catalyst exhibits enhanced ORR performance both in alkaline and acidic solution (half-wave potentials are 0.904 and 0.781 V). This work provides an effective strategy by modulating the local electronic structure and density of FeN4 active sites to improve the ORR activity and stability through Mn cooperation.


Assuntos
Carbono , Oxigênio , Catálise , Oxigênio/química
16.
Small Methods ; 6(6): e2200235, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35484478

RESUMO

Benefitting from outstanding ability of CC reforming and hydrogen activation, nickel is widely applied for heterogeneous catalysis or producing high-quality carbon structures. This high activity simultaneously induces uncontrollable carbon formation, known as coking. However, the activity origin for growing carbon species remains in debate between the on metallic facets induction and nickel carbide segregation. Herein, carbon growth on Ni catalyst is tracked via in situ microscopy methods. Evidence derived from high-resolution transmission electron microscopy imaging, diffraction, and energy loss spectroscopy unambiguously identifies Ni3 C as the active phase, as opposed to metallic Ni nickel or surface carbides as traditionally believed. Specifically, Ni3 C particle grows carbon nanofibers (CNF) layer-by-layer through synchronized oscillation of tip stretch and atomic step fluctuations. There is an anisotropic stress distribution in Ni3 C that provides the lifting force during nanofiber growth. Density functional theory computations show that it is thermodynamically favorable for Ni3 C to decompose into Ni and surface-adsorbed carbon. Carbonaceous deposits aggregate asymmetrically round the particle because partial surface is exposed to the hydrocarbon environment whereas the bottom side is shielded by the support. This induces a carbon concentration gradient within the particle, which drives C migration through Ni3 C phase before it exits as CNF growth.

17.
J Cell Mol Med ; 26(9): 2543-2556, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35411593

RESUMO

The growth of endometrial stromal cells (ESCs) at implantation sites may be a potential factor affecting the success rate of embryo implantation. Incremental proofs demonstrated that ncRNAs (e.g. miRNAs, lncRNAs and circRNAs) were involved in various biological procedures, including proliferation and apoptosis. In this study, the role of miR-100-5p on proliferation and apoptosis of goat ESCs in vitro and embryo implantation in vivo was determined. The mRNA expression of miR-100-5p was significantly inhibited in the receptive phase (RE) rather than in the pre-receptive phase (PE). Overexpression of miR-100-5p suppressed ESCs proliferation and induced apoptosis. The molecular target of MiR-100-5p, HOXA1, was confirmed by 3'-UTR assays. Meanwhile, the product of HOXA1 mRNA RT-PCR increased in the RE more than that in the PE. The HOXA1-siRNA exerted significant negative effects on growth arrest. Instead, incubation of ESCs with miR-100-5p inhibitor or overexpressed HOXA1 promoted the cell proliferation. In addition, Circ-9110 which acted as a sponge for miR-100-5p reversed the relevant biological effects of miR-100-5p. The intrinsic apoptosis pathway was suppressed in ESCs, revealing a crosstalk between Circ-9110/miR-100-5p/HOXA1 axis, PI3K/AKT/mTOR, and ERK1/2 pathways. To further evaluate the progress in study on embryo implantation regulating mechanism of miR-100-5p in vivo, the pinopodes of two phases were observed and analysed, suggesting that, as similar as in situ, miR-100-5p was involved in significantly regulating embryo implantation in vivo. Mechanistically, miR-100-5p performed its embryo implantation function through regulation of PI3K/AKT/mTOR and ERK1/2 pathways by targeting Circ-9110/miR-100-5p/HOXA1 axis in vivo.


Assuntos
MicroRNAs , Fosfatidilinositol 3-Quinases , Regiões 3' não Traduzidas , Animais , Apoptose/genética , Proliferação de Células/genética , Implantação do Embrião/genética , Cabras/genética , Cabras/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Células Estromais/metabolismo , Serina-Treonina Quinases TOR/metabolismo
18.
Cell Death Discov ; 8(1): 185, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35397617

RESUMO

The E3 ubiquitin ligase HECTD3 is homologous with the E6 related protein carboxyl terminus, which plays a vital role in biological modification, including immunoreactivity, drug resistance and apoptosis. Current research indicates that HECTD3 promotes the malignant proliferation of multiple tumors and increases drug tolerance. Our study primarily explored the important function and effects of HECTD3 in gastric cancer. Here, we discovered that HECTD3 is abnormally activated in gastric cancer, and the clinical prognosis database suggested that HECTD3 was strongly expressed in gastric cancer. Depletion of HECTD3 restrained the proliferative and clone abilities of cells and induced the apoptosis of gastric cancer cells. Mechanistically, our findings revealed that interaction between HECTD3 and c-MYC, and that the DOC domain of HECTD3 interacted with the CP and bHLHZ domains of c-MYC. Furthermore, we discovered that HECTD3 mediates K29-linked polyubiquitination of c-MYC. Then, our research indicated that cysteine mutation at amino acid 823 (ubiquitinase active site) of HECTD3 reduces the polyubiquitination of c-MYC. Our experimental results reveal that HECTD3 facilitates the malignant proliferation of gastric cancer by mediating K29 site-linked polyubiquitination of c-MYC. HECTD3 might become a curative marker.

19.
Environ Pollut ; 304: 119252, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35385786

RESUMO

Lead (Pb) exposure can induce DNA damage and alter DNA methylation but their inter-relationships have not been adequately determined. Our overall aims were to explore such relationships and to evaluate underlying epigenetic mechanisms of Pb-induced genotoxicity in Chinese workers. Blood Pb levels (BLLs) were determined and used as individual's Pb-exposure dose and the Comet assay (i.e., % tail DNA) was conducted to evaluate DNA damage. In the screening assay, 850 K BeadChip sequencing was performed on peripheral blood from 10 controls (BLLs ≤100 µg/L) and 20 exposed workers (i.e., 10 DNA-damaged and 10 DNA-undamaged workers). Using the technique, differentially methylated positions (DMPs) between the controls and the exposed workers were identified. In addition, DMPs were identified between the DNA-undamaged and DNA-damaged workers (% tail DNA >2.14%). In our validation assay, methylation levels of four candidate genes were measured by pyrosequencing in an independent sample set (n = 305), including RRAGC (Ras related GTP binding C), USP1 (Ubiquitin specific protease 1), COPS7B (COP9 signalosome subunit 7 B) and CHEK1 (Checkpoint kinase 1). The result of comparisons between the controls and the Pb-exposed workers show that DMPs were significantly enriched in genes related to nerve conduction and cell cycle. Between DNA-damaged group and DNA-undamaged group, differentially methylated genes were enriched in the pathways related to cell cycle and DNA integrity checkpoints. Additionally, methylation levels of RRAGC and USP1 were negatively associated with BLLs (P < 0.05), and the former mediated 19.40% of the effect of Pb on the % tail DNA. These findings collectively indicated that Pb-induced DNA damage was closely related to methylation of genes in cell cycle regulation, and methylation levels of RRAGC were involved in Pb-induced genotoxicity.


Assuntos
Metilação de DNA , Exposição Ocupacional , DNA , Dano ao DNA , Humanos , Chumbo/toxicidade
20.
Front Plant Sci ; 13: 852377, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401630

RESUMO

Gynostemma longipes contains an abundance of dammarane-type ginsenosides and gypenosides that exhibit extensive pharmacological activities. Increasing attention has been paid to the elucidation of cytochrome P450 monooxygenases (CYPs) and UDP-dependent glycosyltransferases (UGTs) that participate downstream of ginsenoside biosynthesis in the Panax genus. However, information on oxidosqualene cyclases (OSCs), the upstream genes responsible for the biosynthesis of different skeletons of ginsenoside and gypenosides, is rarely reported. Here, an integrative study of the metabolome and the transcriptome in the leaf, stolon, and rattan was conducted and the function of GlOSC1 was demonstrated. In total, 46 triterpenes were detected and found to be highly abundant in the stolon, whereas gene expression analysis indicated that the upstream OSC genes responsible for saponin skeleton biosynthesis were highly expressed in the leaf. These findings indicated that the saponin skeletons were mainly biosynthesized in the leaf by OSCs, and subsequently transferred to the stolon via CYPs and UGTs biosynthesis to form various ginsenoside and gypenosides. Additionally, a new dammarane-II synthase (DDS), GlOSC1, was identified by bioinformatics analysis, yeast expression assay, and enzyme assays. The results of the liquid chromatography-mass spectrometry (LC-MS) analysis proved that GlOSC1 could catalyze 2,3-oxidosqualene to form dammarenediol-II via cyclization. This work uncovered the biosynthetic mechanism of dammarenediol-II, an important starting substrate for ginsenoside and gypenosides biosynthesis, and may achieve the increased yield of valuable ginsenosides and gypenosides produced under excess substrate in a yeast cell factory through synthetic biology strategy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...