RESUMO
BACKGROUND: Oral squamous cell cancer (OSCC) is a prevalent malignancy in oral cavity, accounting for nearly 90% of oral malignancies. It ranks sixth among the most common types of cancer worldwide and is responsible for approximately 145,000 deaths each year. It is widely accepted that noncoding RNAs participate cancer development in competitive regulatory interaction, knowing as competing endogenous RNA (ceRNA) network, whereby long non-coding RNA (lncRNA) function as decoys of microRNAs to regulate gene expression. LncRNA FOXD2-AS1 was reported to exert an oncogenic role in OSCC. Nevertheless, the ceRNA network mediated by FOXD2-AS1 was not investigated yet. This study aimed to explore the effect of FOXD2-AS1 on OSCC cell process and the underlying ceRNA mechanism. METHODS: FOXD2-AS1 expression in OSCC cells were determined via reverse transcription and quantitative polymerase chain reaction. Short hairpin RNA targeting FOXD2-AS1 was transfected into OSCC cells to silence FOXD2-AS1 expression. Then, loss-of-function experiments (n = 3 each assay) were performed to measure cell proliferation, apoptosis, migration, and invasion using colony formation, TdT-mediated dUTP Nick-End Labeling, wound healing and Transwell assays, respectively. RNA binding relation was verified by RNA immunoprecipitation and luciferase reporter assays. Rescue experiments were designed to validate whether FOXD2-AS1 affects cell behavior via the gene cellular retinoic acid binding protein 2 (CRABP2). Statistics were processed by GraphPad Prism 6.0 Software and SPSS software. RESULTS: FOXD2-AS1 was significantly upregulated in Cal27 and SCC9 cells (6.8 and 6.4 folds). In response to FOXD2-AS1 knockout, OSCC cell proliferation, migration and invasion were suppressed (approximately 50% decrease) while OSCC cell apoptosis was enhanced (more than two-fold increase). FOXD2-AS1 interacted with miR-378 g to alter CRABP2 expression. CRABP2 upregulation partly rescued (*p < 0.05, **p < 0.01, ***p < 0.001) the inhibitory impact of FOXD2-AS1 depletion on malignant characteristics of OSCC cells. CONCLUSION: FOXD2-AS1 enhances OSCC malignant cell behaviors by interacting with miR-378 g to regulate CRABP2 expression.
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Apoptose , Carcinoma de Células Escamosas , Movimento Celular , Proliferação de Células , MicroRNAs , Neoplasias Bucais , RNA Longo não Codificante , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células/genética , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Staphylococcus arlettae is a rarely reported coagulase-negative staphylococcus (CoNS) isolated from infected humans and livestock. Observing phage-bacteria interaction could improve the understanding of bacterial pathogenetic mechanisms, providing foundational evidence for phage therapy or phage detection. Herein, we aimed to characterise and annotate a novel bacteriophage, vB_SarS_BM31 (BM31), specific to S. arlettae. This bacteriophage was isolated from a milk sample associated with bovine mastitis and collected in the Sichuan Province, China. RESULTS: The BM31 genome comprised a linear double-stranded DNA of 42,271 base pair in length with a G + C content of 34.59%. A total of 65 open reading frames (ORFs) were assembled from phage DNA, of which 29 were functionally annotated. These functional genes were divided into four modules: the structural, DNA packing and replication, lysis, and lysogeny modules. Holin (ORF25), lysin (ORF26), and integrase (ORF28) were located closely in the entire BM31 genome and were important for lyse or lysogeny cycle of BM31. The phage was identified as a temperate phage according to whole genome analysis and life cycle assay, with basic biological characteristics such as small burst size, short latency period, and narrow host range, consistent with the characteristics of the family Siphoviridae, subcluster B14 of the Staphylococcus bacteriophage. CONCLUSIONS: The present isolation and characterisation of BM31 contributes to the Staphylococcus bacteriophage database and provides a theoretical foundation for its potential applications. To the best of our knowledge, BM31 is the only shared and completely reported phage against S. arlettae in the entire public database.
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DNA Viral , Genoma Viral , Animais , Bovinos , Feminino , Humanos , Análise de Sequência de DNA , DNA Viral/genética , DNA Viral/química , Staphylococcus/genética , Fagos de Staphylococcus/genéticaRESUMO
BACKGROUND: Breast cancer is the leading cause of death from cancer in women worldwide. STAMBP functions as a JAMM family deubiquitinating enzyme that modulates the stability of substrate proteins in cells by cleaving ubiquitin moieties. The expression of STAMBP and its clinical significance in breast cancer remain unclear. METHODS AND RESULTS: The level of the STAMBP protein in noncancerous and tumor tissues of breast cancer patients was examined by immunohistochemical staining. The expression of STAMBP mRNA in tissues based on healthy individual and breast cancer patient data in the TCGA database was evaluated. The association between the expression of STAMBP mRNA and clinical features and prognosis was evaluated using TCGA database. Cell growth was assessed by Cell Counting Kit-8 (CCK-8) assay, and cell migration and invasion were assessed by wound healing and Transwell assays. Activation of the ERK signaling was detected by Western blotting. The expression of STAMBP was markedly upregulated in the cytoplasm of tumor cells from breast cancer patients. The level of STAMBP was closely associated with the tumor subtype and size and the TNM stage of the breast cancer patients. Importantly, high expression of STAMBP predicted poor overall survival (OS) for breast cancer patients. Furthermore, knockdown of STAMBP expression reduced cell mobility and invasion of breast cancer cells. Notably, the phosphorylation of EGFR and ERK was markedly reduced in STAMBP-knockdown cells. CONCLUSION: STAMBP plays a critical role in the progression of breast cancer and may serve as a biomarker to monitor the progression of the disease.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Relevância Clínica , Transdução de Sinais/genética , RNA Mensageiro , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismoRESUMO
Single-atom catalysts have attracted attention in the past decade since they maximize the utilization of active sites and facilitate the understanding of product distribution in some catalytic reactions. Recently, this idea has been extended to single-atom nanozymes (SAzymes) for the mimicking of natural enzymes such as horseradish peroxidase (HRP) often used in bioanalytical applications. Herein, it is demonstrated that those SAzymes without constructing the reaction pocket of HRP still undergo the OH radical-mediated pathway like most of the reported nanozymes. Their positively charged single-atom centers resulting from support electronegative oxygen/nitrogen hinder the reductive conversion of H2 O2 to OH radicals and hence display low activity per site. In contrast, it is found that this step can be facilitated over their metallic counterparts on cluster nanozymes with much higher site activity and atom efficiency (cf. SAzymes with 100% atom utilization). Besides the mimicking of HRP in glucose detection, cluster nanozymes are also demonstrated as a better oxidase mimetic for glutathione detection.
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Oxirredutases , Peroxidase , Carbono/química , Domínio Catalítico , PeroxidasesRESUMO
The aims of this article were to investigate Bacillus safensis HL3 spore for its capacity to degrade and detoxify indigo carmine and to provide an effective biological agent for the treatment of isatin dye wastewater. Bacillus safensis HL3 spore was found to decolorize indigo carmine by 97% in the presence of acetosyringone within 2 h. Significantly increased activities of spore laccase, intracellular tyrosinase, and lignin peroxidase upon exposure to indigo carmine were observed. The results of RT-qPCR also showed that the expression of laccase gene was significantly increased. The spore has the ability to degrade indigo carmine through oxidization. Furthermore, the pathway by which indigo carmine is degraded was investigated using liquid chromatography-mass spectrometry analysis to identify the biodegradation products. A detailed pathway of indigo carmine degradation by bacterial spores was proposed for the first time. Toxicity tests indicated that the biodegradation products of indigo carmine are non-toxic to Nicotiana tabacum seeds and are less hazardous to human erythrocytes than the original dye. Indigo carmine is a typical recalcitrant dye and severely jeopardizes human health. The results demonstrate the utility of the spore from Bacillus safensis HL3 for the degradation of indigo carmine and simultaneous reduction of its toxicity.
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Bacillus , Índigo Carmim , Humanos , Bacillus/metabolismo , Biodegradação Ambiental , Lacase/metabolismo , Corantes/químicaRESUMO
It is known that the interplay between molecules and active sites on the topmost surface of a solid catalyst determines its activity in heterogeneous catalysis. The electron density of the active site is believed to affect both adsorption and activation of reactant molecules at the surface. Unfortunately, commercial X-ray photoelectron spectroscopy, which is often adopted for such characterization, is not sensitive enough to analyze the topmost surface of a catalyst. Most researchers fail to acknowledge this point during their catalytic correlation, leading to different interpretations in the literature in recent decades. Recent studies on pristine Cu2 O [Nat. Catal. 2019, 2, 889; Nat. Energy 2019, 4, 957] have clearly suggested that the electron density of surface Cu is facet dependent and plays a key role in CO2 reduction. Herein, it is shown that pristine CeO2 can reach 2506/1133 % increase in phosphatase-/peroxidase-like activity if the exposed surface is wisely selected. By using NMR spectroscopy with a surface probe, the electron density of the surface Ce (i.e., the active site) is found to be facet dependent and the key factor dictating their enzyme-mimicking activities. Most importantly, the surface area of the CeO2 morphologies is demonstrated to become a factor only if surface Ce can activate the adsorbed reactant molecules.
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Cério , Isoenzimas/química , Adsorção , Catálise , Cério/química , Oxirredução , Espectroscopia FotoeletrônicaRESUMO
The emission characteristics of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and heavy metals were evaluated during co-combustion of sewage sludge with coal from a circulating fluidized bed incinerator. The stack gas, slag and fly ash samples were sampled and analyzed. The gas-cleaning system consisted of electrostatic precipitators and a semi-dry scrubber. Results showed that the stack gas and fly ash exhibited mean dioxin levels of 9.4 pg I-TEQ/Nm3 and 11.65 pg I-TEQ/g, respectively, and showed great similarities in congener profiles. By contrast, the slag presented a mean dioxin level of 0.15 pg I-TEQ/g and a remarkable difference in congener profiles compared with those of the stack gas and fly ash. Co-combusting sewage sludge with coal was able to reduce PCDD/Fs emissions significantly in comparison with sewage sludge mono-combustion. The leaching levels of Hg, Pb, Cd, Ni, Cr, Cu, and As in the fly ash and slag were much lower than the limits of the environmental protection standard in China. These suggest that the co-combustion of sewage sludge and coal is an advisable treatment method from an environmental perspective.
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Benzofuranos/análise , Esgotos , Cádmio/análise , Cobre/análise , Dibenzofuranos Policlorados , Chumbo/análise , Mercúrio/análise , Metais Pesados/análise , Níquel/análiseRESUMO
The p53 tumor suppressor exerts antitumor functions through its ability to regulate the transcription of its downstream targets. Long noncoding RNAs (lncRNAs) act as oncogenes or tumor suppressors implicated in tumorigenesis and tumor progression. Here, we identify the lncRNA LINC00324 (long intergenic noncoding RNA 00324) as a direct p53 transcriptional target. Knockdown of LINC00324 expression promotes tumor growth by reducing p53 transcriptional activity, whereas ectopic LINC00324 expression demonstrates a reverse effect. Notably, LINC00324 is present in the endogenous p53 complex in tumor cells and directly binds to the C-terminal domain of p53 in vitro. Mechanistically, LINC00324 enables p53 transactivation by competitively disrupting the p53-SET interaction, resulting in an increase of p300/CBP-mediated H3K18 and H3K27 acetylation on the p53 target promoters. Lower LINC00324 expression is associated with more aggressive disease status and predicts worse overall survival of patients with cancer. Our study identifies a p53/LINC00324 positive feedback loop that suppresses tumor growth by counteracting SET-mediated transcriptional repression.
Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , Retroalimentação , Expressão Gênica , Neoplasias/genética , Oncogenes , RNA Longo não Codificante/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
The Millennium Ecosystem Assessment (MA) framework was modified with a special focus on ecosystem service values. A case study of a typical low-carbon industrial park in Beijing was conducted to assess the ecological and economic benefits. The total economic value of this industrial park per year is estimated to be 1.37 × 10(8) RMB yuan, where the accommodating and social cultural services are the largest two contributors. Due to the construction of small grasslands or green roofs, considerable environmental regulation services are also provided by the park. However, compared with an ecoindustrial park, carbon mitigation is the most prominent service for the low-carbon industrial park. It can be concluded that low-carbon industrial park construction is an efficacious way to achieve coordinated development of society, economy, and environment, and a promising approach to achieving energy saving and carbon reduction.
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Ecologia/economia , Ecossistema , Resíduos Industriais , Gerenciamento de Resíduos/economia , Algoritmos , Carbono/economia , Carbono/metabolismo , Dióxido de Carbono/economia , Dióxido de Carbono/metabolismo , China , Conservação dos Recursos Naturais/economia , Conservação dos Recursos Naturais/métodos , Conservação dos Recursos Naturais/tendências , Ecologia/métodos , Ecologia/tendências , Meio Ambiente , Indústrias/economia , Indústrias/métodos , Indústrias/tendências , Modelos Econômicos , Gerenciamento de Resíduos/métodosRESUMO
Samples of sewage, well water, and underground river water of the urbanized Laolongdong karst underground river basin in Chongqing, China were collected during July 2019 and October 2020 and measured to determine the nitrate origin and biogeochemical processes based on geochemistry and dual nitrate isotope (δ15N-NO3- and δ18O-NO3-) data. The results showed that:â the isotopic nitrate compositions of sewage ranged from -3.3 to 14.6 for δ15N-NO3- and from -5.2 to 20.6 for δ18O-NO3-, which indicated that nitrate originated from manure and sewage, fertilizer, and soil organic nitrogen. The δ15N-NO3- and δ18O-NO3- of well water varied from 3.1 to 12.6 and 2.9 to 8.9, respectively, suggesting nitrate was mainly from soil organic nitrogen and manure and sewage. For the underground river water, the δ15N-NO3- and δ18O-NO3- ranged from 5.6 to 28.6 and from -2.0 to 15.7, respectively, suggesting that municipal sewage and manure were the dominate nitrate sources. â¡ Based on the MixSIAR model, manure and sewage were the primary nitrate source of the underground river water, accounting for 89.1% of the total contribution, whereas the contributions of soil organic nitrogen, fertilizer, and atmospheric precipitation were 4.4%, 3.4%, and 3.1%, respectively. ⢠In the basin, the concentration ratios of COD:ρ(NO3-) from low to high were as follows:well water (0.14-5.15), underground river water (0.50-9.36), and sewage (4.08-89.50). Only 50% of well water samples with COD:ρ(NO3-) were slightly higher than 0.65, which is the minimum stoichiometric ratio for denitrification occurrence. This indicated that there were insufficient COD concentrations to support that denitrification occurred in the well water. This was further verified by no significant enrichment of nitrogen and oxygen isotopes. As much as 90% of underground river water samples had a COD:ρ(NO3-) higher than 0.65, and the dual nitrate isotopes were simultaneously enriched with a δ15N:δ18O of 1.8, which is within the ratios ranging from 1.3 to 2.1, indicating that denitrification occurred. The COD:ρ(NO3-) for all wastewater samples was much higher than 0.65, of which 25% were higher than the stoichiometric ratio (29.34) for the occurrence of dissimilation reduction nitrate to ammonium (DNRA). The δ15N-NO3- and ρ(NH4+):ρ(NO3-) of sewage increased simultaneously, indicating that DNRA may have occurred in the sewage.
Assuntos
Compostos de Amônio , Água Subterrânea , Poluentes Químicos da Água , Monitoramento Ambiental/métodos , Fertilizantes/análise , Esterco , Nitratos/análise , Nitrogênio/análise , Isótopos de Nitrogênio/análise , Óxidos de Nitrogênio , Isótopos de Oxigênio/análise , Rios/química , Esgotos/química , Solo/química , Águas Residuárias , Água , Poluentes Químicos da Água/análiseRESUMO
Ascorbic acid (AsA) is an important nutritious substance in fruits, and it also can maintain the biological activity of fruits during storage. This research investigated the effect of exogenous melatonin (MT) on AsA metabolism in postharvest kiwifruit. Our results indicated that exogenous MT delayed the decrease of fruit firmness and titratable acid (TA), inhibited the increase of soluble solids content (SSC), reduced the respiration rate and ethylene production, and maintained a higher AsA content in kiwifruit during storage. The high expression of L-galactose pathway key genes in the early storage and regeneration genes in the later storage maintained the AsA content in postharvest kiwifruit. MT treatment enhanced the expression levels of AsA biosynthesis (AcGME2, AcGalDH, and AcGalLDH) and regeneration (AcGR, AcDHAR, and AcMDHAR1) genes. Meanwhile, the expression of the degradation gene AcAO was inhibited in MT-treated kiwifruits.
RESUMO
With the improper use of antibiotics, an increasing number of multidrug-resistant bacteria have been reported worldwide, posing challenges for disease treatment. Klebsiella pneumoniae is an important zoonotic pathogen that colonises the respiratory tract. Endolysin therapy has emerged with the development of phages. In this study, a lytic phage vB_KpnS_MK54 was isolated from the drinking water of a forest musk deer (FMD) farm in Sichuan Province. It was the first reported phage obtained from FMD. The primary biological characteristics were determined, and whole-genome sequencing analysis was performed. The phage which belongs to the family Siphoviridae is highly specific for lytic host bacteria and is moderately adaptable to different environments. Whole-genome sequencing results showed that the phage genome size was 46,218 bp. There were 80 coding DNA sequences (CDSs) in total, 32 of which had known functions. The last CDS is the phage endolysin LysG24. A new peptide-modified endolysin (LysCA) was constituted by connecting the cecropin A peptide residues with LysG24 to investigate the antibacterial activities of both LysG24 and LysCA. The results showed that the lytic profile of LysG24 and LysCA was wider than that of phage MK54. For in vitro tests, both endolysins destroyed 99% of the host bacteria within 6 h. The lysing ability and environmental adaptability of LysCA were significantly stronger than those of LysG24. For in vivo tests, LysG24 and LysCA exhibited therapeutic effects in a mouse model of pneumonia wherewith the mice were infected with K. pneumoniae (LPKP), wherein both LysG24 and LysCA can effectively reduce the pulmonary inflammatory response. The LPKP bacterial load in the treatment group was significantly lower than that in the bacterial group, among which LysCA displayed a more obvious therapeutic effect. Furthermore, the safety test showed that the endolysins had no toxic effects on mice. In general, both LysG24 and LysCA showed excellent antibacterial activity in vivo and in vitro, with high safety and strong adaptability to the environment, manifesting their latent potential as new antimicrobial agents.
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Bovine mastitis is a common disease occurring in dairy farms and can be caused by more than 150 species of pathogenic bacteria. One of the most common causative organisms is Streptococcus agalactiae, which is also potentially harmful to humans and aquatic animals. At present, research on S. agalactiae in China is mostly concentrated in the northern region, with limited research in the southeastern and southwestern regions. In this study, a total of 313 clinical mastitis samples from large-scale dairy farms in five regions of Sichuan were collected for isolation of S. agalactiae. The epidemiological distribution of S. agalactiae was inferred by serotyping isolates with multiplex polymerase chain reaction. Susceptibility testing and drug resistance genes were detected to guide the clinical use of antibiotics. Virulence genes were also detected to deduce the pathogenicity of S. agalactiae in Sichuan Province. One hundred and five strains of S. agalactiae (33.6%) were isolated according to phenotypic features, biochemical characteristics, and 16S rRNA sequencing. Serotype multiplex polymerase chain reaction analysis showed that all isolates were of type Ia. The isolates were up to 100% sensitive to aminoglycosides (kanamycin, gentamicin, neomycin, and tobramycin), and the resistance rate to ß-lactams (penicillin, amoxicillin, ceftazidime, and piperacillin) was up to 98.1%. The TEM gene (ß-lactam-resistant) was detected in all isolates, which was in accordance with a drug-resistant phenotype. Analysis of virulence genes showed that all isolates harbored the cfb, cylE, fbsA, fbsB, hylB, and α-enolase genes and none harbored bac or lmb. These data could aid in the prevention and control of mastitis and improve our understanding of epidemiological trends in dairy cows infected with S. agalactiae in Sichuan Province.
Assuntos
Mastite Bovina , Infecções Estreptocócicas , Animais , Antibacterianos/farmacologia , Bovinos , Resistência Microbiana a Medicamentos , Feminino , Humanos , Mastite Bovina/epidemiologia , Mastite Bovina/microbiologia , Tipagem Molecular , Prevalência , RNA Ribossômico 16S , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae , Virulência/genética , Fatores de Virulência/genéticaRESUMO
Tumor metastasis is a leading cause of death in lung adenocarcinoma (LUAD) patients, but the molecular events that regulate metastasis have not been completely elucidated. STAMBP is a deubiquitinating enzyme of the Jab1/MPN metalloenzyme family that regulates the stability of substrates in cells by specifically removing ubiquitin molecules. We found that STAMBP expression was increased in the cytoplasm of tumor cells from LUAD patients. The STAMBP level was closely associated with tumor size, lymph node invasion and neoplasm disease stage. A high STAMBP level predicted poor overall survival and disease-free survival in LUAD patients. STAMBP overexpression promoted cell migration and invasion, whereas STAMBP knockdown attenuated these processes in LUAD cells after epidermal growth factor treatment. Mechanistically, increased STAMBP expression promoted the stabilization of Epidermal growth factor receptor (EGFR), whereas STAMBP knockdown induced the degradation of EGFR. STAMBP may deubiquitinate EGFR by localizing in early endosomes and increase EGFR membrane localization in LUAD cells. The overexpression of STAMBP triggered the activation of MAPK signaling after epidermal growth factor treatment. In contrast, this activation was attenuated in STAMBP knockdown cells. Small molecule inhibitors of EGFR and MAPK signaling pathway may block STAMBP-induced cell mobility and invasion as well as ERK activation in cells. Importantly, STAMBP knockdown suppressed LUAD tumor growth and metastasis by regulating the EGFR-mediated ERK activation in a xenograft mouse model. Our findings identified STAMBP as a novel potential target for LUAD therapy.
Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais , Ubiquitina Tiolesterase/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Modelos Animais de Doenças , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Endossomos/metabolismo , Receptores ErbB/metabolismo , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/farmacologia , Transporte Proteico , Transdução de Sinais/efeitos dos fármacos , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Lung cancer is the second most common cancer in both men and women. The deubiquitinase PSMD7, as a core component of the 26S proteasome, is critical for the degradation of ubiquitinated proteins in the proteasome. Currently, PSMD7 expression and its roles in the progression of lung cancer remain largely unknown. In this study, we assessed PSMD7 expression and investigated the underlying molecular events by which PSMD7 regulates tumor progression in non-small cell lung cancer (NSCLC). The results showed that PSMD7 is more highly expressed in NSCLC tissues than in adjacent noncancerous tissues. PSMD7 expression was also closely associated with lymph node invasion and the laterality of the tumor in lung adenocarcinoma (LUAD). A high PSMD7 level predicted poor overall survival (OS) and disease-free survival (DFS) in LUAD patients, and PSMD7 knockdown significantly reduced cell proliferation and induced G0/G1-phase cell cycle arrest, cell senescence and apoptosis. PSMD7 knockdown inhibited expression of a set of proteins regulating cell cycle progression. Depletion of PSMD7 increased p53 levels and induced p21 and puma expression in a p53-dependent manner. Importantly, knockdown of PSMD7 markedly inhibited LUAD tumor growth in a xenograft mouse model. Taken together, these findings indicate that PSMD7 may serve as a valuable prognostic indicator and potential therapeutic target in LUAD.
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Although H2O2 has been often employed as a green oxidant for many CeO2-catalyzed reactions, the underlying principle of its activation by surface oxygen vacancy (Vo) is still elusive due to the irreversible removal of postgenerated Vo by water (or H2O2). The metastable Vo (ms-Vo) naturally preserved on pristine CeO2 surfaces was adopted herein for an in-depth study of their interplay with H2O2. Their well-defined local structures and chemical states were found facet-dependent affecting both the adsorption and subsequent activation of H2O2. It is concluded that a strong adsorption of H2O2 on ms-Vo may not guarantee its subsequent activation. The ms-Vo can be only free for the next catalytic cycle when the electron density of surface Ce is high enough to reduce/break the O-O bond of adsorbed H2O2. This explains the 211.8 and 35.8 times enhancement in H2O2 reactivity when the CeO2 surface is changed from (111) and (110) to (100).
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Breast cancer is the most common malignant tumor and the leading cause of cancer-related death in women. The ubiquitin-proteasome system regulates the stability of most proteins controlling various biological processes in human cells. PSMD7, as a core component of the 26S proteasome, is critical for the degradation of ubiquitinated proteins in the proteasome. Currently, PSMD7 expression and its roles in the progression of breast cancer remain largely unknown. In this study, we assessed the level of PSMD7 in breast cancer tissues and investigated the underlying molecular events by which PSMD7 could play a role in tumor progression. The results showed that the PSMD7 level was significantly upregulated in breast cancer tissues. PSMD7 expression was closely associated with tumor subtype, tumor size, lymph node invasion, and TNM stage. A high PSMD7 level predicted poor overall survival (OS) and disease-free survival (DFS) in breast cancer patients. Furthermore, univariate Cox regression analysis indicated that lymph node invasion, distant metastasis, and PSMD7 expression were associated with OS and DFS. Multivariate regression analysis indicated that PSMD7 was an independent predictor of OS (HR=1.310, 95% CI=1.038-1.652). Importantly, PSMD7 knockdown induced cell cycle arrest in the G0/G1 phase, leading to cell senescence and apoptosis. PSMD7 knockdown inhibited the expression of key cell cycle-related proteins and promoted the stability of p21 and p27 in breast cancer cells. PSMD7 may be a valuable prognostic indicator and potential therapeutic target for breast cancer.
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Lung cancer is one of the most common malignant tumors in the world, with a high rate of malignancy and mortality. Seeking new biomarkers and potential drug targets is urgent for effective treatment of the disease. Deubiquitinase UCHL5/UCH37, as an important component of the 26S proteasome, plays critical roles in ubiquitinated substrate degradation. Although previous studies have shown that UCHL5 promotes tumorigenesis, its role in lung cancer remains largely unknown. In this study, we evaluated the expression and clinical significance of UCHL5 in non-small cell lung cancer (NSCLC). The results demonstrated that the UCHL5 expression level was significantly upregulated in NSCLC tissues compared with the adjacent noncancerous tissues. The level of UCHL5 was associated with tumor size, lymph node invasion, TNM stage and malignant tumor history in patients with lung adenocarcinoma (LUAD). Importantly, high UCHL5 expression predicted a poor overall survival (OS) and a poor disease-free survival (DFS) in patients with LUAD. Univariate regression analysis showed that tumor size, lymph node invasion, TNM stage and UCHL5 expression were associated with OS and DFS in patients with LUAD. The multivariate analysis indicated that the UCHL5 expression level was an independent prognostic factor for OS (HR=1.171, 95% CI=1.052-1.303) and DFS (HR=1.143, 95% CI=1.031-1.267) in these patients. UCHL5 knockdown in LUAD cells significantly inhibited cell proliferation and reduced the expression of key cell cycle proteins. These findings indicate that UCHL5 may serve as a potential prognostic marker and a new therapeutic target for patients with LUAD.
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PSMD14 is a 19S-proteasome-associated deubiquitinating enzyme that facilitates protein degradation by the 20S proteasome core particle. Although accumulating evidence indicates that PSMD14 has emerged as a critical oncogenic factor by promoting tumor growth, the expression and function of PSMD14 in non-small cell lung cancer (NSCLC) remain largely unknown. In this study, we assessed PSMD14 expression and correlated it with clinical-pathological features and patient survival in NSCLC. We also determined the roles of PSMD14 in the regulation of lung adenocarcinoma (LUAD) cell growth. The results showed that PSMD14 expression was significantly upregulated in human NSCLC tissues compared with adjacent non-cancerous tissues. The PSMD14 level was associated with tumor size, lymph node invasion, and TNM stage in LUAD patients. Importantly, high PSMD14 expression was associated with poor overall survival (OS) and disease-free survival (DFS) in LUAD patients. Further, knockdown of PSMD14 significantly inhibited cell growth and caused G1 arrest and cellular senescence by increasing p21 stability in LUAD cells. PSMD14 knockdown also promoted cell apoptosis by increasing cleaved caspase-3 levels in H1299 cells. PSMD14 may serve as a potential prognostic marker and therapeutic target for LUAD patients.
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We demonstrate that the Ce reactivity of CeO2 towards H2O2 is dictated by its local structure and electron density. More than 2400% increase in peroxidase-like activity has been achieved on the (100) surface for glucose detection due to the promoted H2O2 adsorption and subsequent activation by the electron-rich Ce species.