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1.
Artigo em Inglês | MEDLINE | ID: mdl-38290458

RESUMO

Objective: To study the association of H. pylori infection with colorectal adenomas. Methods: Web searches of PubMed, Embase, and Scopus databases for randomized controlled trials, class-experimental studies, and cohort studies on the association between H. pylori and colorectal adenomas were performed from May 2000 to May 2023. Literature was screened based on inclusion and exclusion criteria, data were extracted and evaluated for quality, and statistical analyses were performed using RevMan 5.2 software. Results: A total of 15 studies were included, and meta-analysis showed a statistically significant difference between colorectal neoplastic polyp cases in the H. pylori-positive and H. pylori-negative groups [OR=1.80, 95%CI: (1.31, 2.47), P < .01, I2 = 95%]. Analysis based on subgroups of different H. pylori detection methods showed that the correlation between H. pylori infection and colorectal polyp incidence is not affected by their detection methods, with serological detection subgroup: [OR=0.13, 95%CI: (0.05, 0.21), P < .01, I2 = 88%], and non-serological detection subgroup: [OR=0.13, 95%CI: (0.04, 0.22), P < .01, I2 = 95%]. Subgroup analysis of pathological types showed that H. pylori infection is not significantly associated with the development of non-neoplastic polyps [OR=1.47, 95%CI: 0.98-2.22, P = .06], whereas it is correlated with the development of neoplastic polyps [95%CI: 1.69-3.22, P < .01]. In the subgroup analysis of geographic differences in the population, H. pylori infection was correlated with the development of colorectal polyps in different geographic populations (P < .01). Conclusion: H. pylori infection is a risk factor for colorectal polyp neoplasia, its infection is associated with colorectal neoplasia, and the correlation is not affected by the different methods of H. pylori detection and the different geographic regions of the population.

2.
Reprod Domest Anim ; 58(5): 657-661, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36808762

RESUMO

In the current study, the difference between the sex-sorted and non-sex-sorted frozen semen of Holstein Friesian breed cattle was investigated. Significant variation (p < .05) was found in the semen quality parameters such as motility; vitality; acrosome integrity rate; the anti-oxidative enzyme activity including GSH (glutathione); SOD (superoxide dismutase); CAT (catalase); GSH-Px (glutathione peroxidase) and the rate of fertilization. The results showed that the sperm acrosome integrity and motility of the non-sorted sperm were higher compared to sex-sorted sperm (p < .05). The linearity index and mean coefficient analysis revealed that the percentage of 'grade a' in sex-sorted sperm were significantly (p < .05) lower than non-sorted sperm. Interestingly, low SOD level and high CAT level was found in the non-sexed semen than in the sexed semen (p < .05). Furthermore, the GSH and GSH-Px activity in the sexed semen was found lower than the non-sexed semen (p < .05). In conclusion, sperm motility characteristics were lower in sex-sorted semen than in non-sex-sorted semen. This might be related to the complex process of sexed semen production, which could reduce sperm motility and movement characteristics, acrosomal integrity, CAT, SOD, GSH and GSH-Px, and finally lead to the decline in the fertilization rate.


Assuntos
Preservação do Sêmen , Sêmen , Bovinos , Masculino , Animais , Análise do Sêmen/veterinária , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Motilidade dos Espermatozoides , Criopreservação/veterinária , Criopreservação/métodos , Espermatozoides , Glutationa , Superóxido Dismutase
3.
Sensors (Basel) ; 23(16)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37631627

RESUMO

Traffic management is a critical task in software-defined IoT networks (SDN-IoTs) to efficiently manage network resources and ensure Quality of Service (QoS) for end-users. However, traditional traffic management approaches based on queuing theory or static policies may not be effective due to the dynamic and unpredictable nature of network traffic. In this paper, we propose a novel approach that leverages Graph Neural Networks (GNNs) and multi-arm bandit algorithms to dynamically optimize traffic management policies based on real-time network traffic patterns. Specifically, our approach uses a GNN model to learn and predict network traffic patterns and a multi-arm bandit algorithm to optimize traffic management policies based on these predictions. We evaluate the proposed approach on three different datasets, including a simulated corporate network (KDD Cup 1999), a collection of network traffic traces (CAIDA), and a simulated network environment with both normal and malicious traffic (NSL-KDD). The results demonstrate that our approach outperforms other state-of-the-art traffic management methods, achieving higher throughput, lower packet loss, and lower delay, while effectively detecting anomalous traffic patterns. The proposed approach offers a promising solution to traffic management in SDNs, enabling efficient resource management and QoS assurance.

4.
Trop Anim Health Prod ; 56(1): 19, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110604

RESUMO

In the current study, the role of the ovine IGF2 as a potential candidate gene was investigated as though marker-assisted selection in Chinese Tibetan sheep. The Sanger DNA sequencing method explored five single nucleotide polymorphisms (SNPs) in 5'UTR of the ovine IGF2 gene (C15640T, G15801A, G15870A, C15982G and G15991A) in Chinese Tibetan sheep. The frequencies of four SNPs were within the Hardy-Weinberg Equilibrium (chi-square test) except C15982G. The statistical analysis indicated that the C15640T and G15801A were significantly associated with body height, body length, chest circumference, and body weight (P < 0.05 or P < 0.01). Furthermore, C15982G variant exhibited significant correlation with the body weight (P < 0.01). These findings suggests that the promoter variants of IGF2 gene could be used as a candidate gene through marker-assisted selection for the body weight and body measurement traits in Tibetan sheep breeding program.


Assuntos
Peptídeos Semelhantes à Insulina , Polimorfismo de Nucleotídeo Único , Ovinos/genética , Animais , Tibet , Fenótipo , Peso Corporal/genética , Genótipo
5.
J Fish Dis ; 45(7): 1033-1043, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35475515

RESUMO

Largemouth bass ranavirus disease (LMBVD) caused by largemouth bass ranavirus (LMBV) has resulted in severe economic losses in the largemouth bass (Micropterus salmoides) farming industry in China. Early and accurate diagnosis is the key measure for the prevention and control of LMBVD. In this study, a quantitative polymerase chain reaction (qPCR) and a real-time recombinase-aided amplification (real-time RAA) assay were established for the detection of LMBV. The sensitivity and specificity of these two methods, and the efficacy for detection of LMBV from clinical samples were also evaluated. Results showed that the real-time RAA reaction was completed in <30 min at 39℃ with a detection limit of 58.3 copies, while qPCR reaction required 60 min with a detection limit of 5.8 copies. Both methods were specific for LMBV, where no cross-reactions observed with the other tested fish pathogens. Comparing the amplification results of both assays to the results obtained by virus isolation using 53 clinical tissue samples, results showed that the clinical sensitivity of real-time RAA and qPCR were 93.75% and 100% respectively, and the clinical specificity of both were 100%. Our results showed that qPCR is more suitable for quantitative analysis and accurate detection of LMBV in the laboratory, while real-time RAA is more suitable as a point-of-care diagnostic tool for on-site detection and screening of LMBV under farm conditions and in poorly equipped laboratories.


Assuntos
Bass , Infecções por Vírus de DNA , Doenças dos Peixes , Ranavirus , Animais , Infecções por Vírus de DNA/diagnóstico , Infecções por Vírus de DNA/veterinária , Doenças dos Peixes/diagnóstico , Ranavirus/genética , Recombinases , Sensibilidade e Especificidade
6.
Mol Carcinog ; 59(10): 1174-1187, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32805084

RESUMO

Long noncoding RNAs (LncRNAs) have emerged as important players in cancer biology. Increasing evidence suggests that LncRNAs are frequently dysregulated in cancer and may function as oncogenes or tumor suppressors. Urothelial carcinoma associated 1 (UCA1), a LncRNA, firstly identified in bladder transitional cell carcinoma, seems to act as an oncogene in many different types of human cancers by promoting cell proliferation and migration. In this study, we revealed a novel biological function of UCA1, which was different from that reported by previous studies, was responsible for maintaining the low-tumorigenic, nonmetastatic phenotypes in primary prostate epithelial cells. UCA1 could stabilize E-cadherin protein by preventing the interaction between E-cadherin and its E3 ligase MDM2, which suppressed MDM2-mediated ubiquitination and degradation of E-cadherin. In addition, we also found that UCA1 acted as a sponge of miR-296-3p, which targeted E-cadherin gene CDH1 messenger RNA at the posttranscription level. Taken together, these findings demonstrated that UCA1 had a new important role in effectively keeping E-cadherin at a high level through a dual mechanism, which maintained primary prostate cancer cells at the low-tumorigenic and nonmetastatic status.


Assuntos
Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias da Próstata/patologia , RNA Longo não Codificante/genética , Animais , Antígenos CD/genética , Apoptose , Biomarcadores Tumorais/genética , Caderinas/genética , Proliferação de Células , Humanos , Masculino , Camundongos , Camundongos SCID , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
7.
J Autoimmun ; 89: 125-138, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29269245

RESUMO

Rho-associated kinase (ROCK) has been found to be involved in the pathogenesis of a variety of autoimmune diseases, but the role of ROCK in inflammatory bowel disease (IBD) is still elusive. In this study, we demonstrated that the levels of ROCK2, but not ROCK1, activity were significantly upregulated in peripheral blood mononuclear cells (PBMC) and inflamed mucosa from IBD patients using a ROCK activity assay, and that ROCK2 activity in intestinal mucosa was positively correlated with disease severity. Stimulation with TNF markedly upregulated ROCK2 activity in IBD CD4+ T cells through NF-κB signaling. Blockade of ROCK2 activity using Slx-2119 significantly suppressed proinflammatory cytokines in inflamed mucosa from IBD patients including IFX-unresponsive CD patients, and inhibited IBD CD4+ T cells to differentiate into Th1 and Th17 cells through downregulating phosphorylated Stat1 and Stat3, but promoted Treg cell differentiation through upregulating phosphorylated Stat5. Furthermore, oral administration of Slx-2119 markedly ameliorated intestinal mucosal inflammation in TNBS-induced colitis in mice and decreased proinflammatory cytokines productions in inflamed colon. Our data indicate that ROCK2 plays a critical role in inducing mucosal T cell activation and inflammatory responses in IBD and that inhibition of ROCK2 activity might serve as a novel therapeutic approach in the management of IBD.


Assuntos
Colite/imunologia , Inflamação/imunologia , Doenças Inflamatórias Intestinais/imunologia , Mucosa Intestinal/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Quinases Associadas a rho/metabolismo , Adulto , Animais , Diferenciação Celular , Células Cultivadas , Colite/induzido quimicamente , Modelos Animais de Doenças , Feminino , Humanos , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Transdução de Sinais , Adulto Jovem
8.
J Fish Dis ; 41(12): 1811-1819, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30255607

RESUMO

Currently, serological assays for grass carp reovirus genotype II (GCRV-II) diagnosis are not available. In this study, an indirect enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against GCRV-II was developed. The structural protein VP38 of GCRV-II was used as the coating antigen. Monoclonal antibodies (mAb) against IgM of grass carp labelled with HRP were used as a secondary antibody. The antigen concentration and serum dilution were optimized using chess board titration. Furthermore, the specificity of indirect ELISA assay was confirmed by cross check with sera positive for other grass carp pathogens. In comparison with results obtained from indirect immunofluorescence assay (IFA) and Western blot by testing of 60 serum samples to evaluate the sensitivity and specificity of the ELISA, agreement between 90% and 96.7% was reached, respectively. A serological survey was performed using the assay with grass carp field serum samples. The seropositive rate of the 242 serum samples was 69.8%. In conclusion, the developed indirect ELISA is a very specific and sensitive test that will be useful for large-scale serological surveys to detect indirectly GCRV II infections as well as to monitor the changes of antibody level after immunization.


Assuntos
Anticorpos Antivirais/isolamento & purificação , Western Blotting/veterinária , Ensaio de Imunoadsorção Enzimática/veterinária , Doenças dos Peixes/diagnóstico , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Infecções por Reoviridae/veterinária , Reoviridae/isolamento & purificação , Animais , Western Blotting/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Doenças dos Peixes/virologia , Técnica Indireta de Fluorescência para Anticorpo/métodos , Proteínas Recombinantes/metabolismo , Infecções por Reoviridae/diagnóstico , Infecções por Reoviridae/virologia , Sensibilidade e Especificidade , Proteínas Virais/metabolismo
9.
Biochem Biophys Res Commun ; 485(1): 95-101, 2017 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-28189685

RESUMO

LRSAM1, a RING-type E3 ubiquitin ligase, is essential for regulating cargo sorting, signaling pathways, cell adhesion and anti-bacterial autophagy. It is important to elucidate the mechanism that underlies the regulation of LRSAM1 E3 ligase activity. Here, we reported that LRSAM1 exhibited self-association in vitro and in vivo. We found the self-association of LRSAM1 promotes intermolecular ubiquitination and proved a potential N-terminal ubiquitination. The E3 activity of LRSAM1 is amplified when the RING domain is present in tandem with its N-terminal domain(s). Furthermore, we found that the CC2-SAM domain had a strong inhibitory effect on the E3 activity of LRSAM1 in vitro and blocked ubiquitination of TSG101 in vivo; the tandem CC1 domain, but not the individual CC1 domain, could counteract this inhibition. Collectively, our data characterized the self-association of LRSAM1 and showed how its domains may contribute to its overall activity.


Assuntos
Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Células HEK293 , Células HeLa , Humanos , Domínios Proteicos , Ubiquitina-Proteína Ligases/química
10.
Protein Expr Purif ; 129: 158-161, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27154902

RESUMO

LRSAM1 is a typical RING-finger E3 ubiquitin ligase that plays an important role in many processes. The expression and purification of LRSAM1 from Escherichiacoli had not yet been reported. Here, strategies to clone, express and purify recombinant LRSAM1 in E. coli cells were developed. LRSAM1 was expressed with high yield as inclusion bodies and successfully recovered in soluble form by subsequent denaturation and renaturation steps. Refolded LRSAM1 was directly purified through two steps of ammonium sulfate precipitation, resulting in a purity of up to 95% and a yield of about 6 mg/L bacterial culture. Purified recombinant LRSAM1 exhibited a pH-dependent E3 ligase activity. Its ligase activity was RING-finger domain-dependent, and its ubiquitination favors K6-, K27-, K29- and K48-linkages in cooperation with UbcH5-type E2 enzymes.


Assuntos
Escherichia coli/metabolismo , Expressão Gênica , Ubiquitina-Proteína Ligases , Escherichia coli/genética , Células HeLa , Humanos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Ubiquitina-Proteína Ligases/biossíntese , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/isolamento & purificação , Ubiquitinação
11.
Dig Dis ; 34(1-2): 90-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26982193

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by excessive immune responses to altered intestinal microbiota in genetically susceptible individuals. The diagnosis of IBD depends on clinical, endoscopic, histological, radiological and biochemical criteria, which may be invasive, time consuming and usually not accepted by patients with IBD. KEY MESSAGES: Serological biomarkers have been demonstrated to be a series of rapid, non-invasive approaches for assessments of early diagnosis, disease activity and prognosis for IBD. Importantly, serum antibodies against microbial antigens or auto-antigens have been used as biomarkers in predicting disease course, complications and responses to medications and surgery. Moreover, they have been demonstrated to be useful in distinguishing patients with Crohn's disease (CD) from those with ulcerative colitis (UC). Recently, a great number of new serum biomarkers (e.g., anti-glycoprotein 2, anti-granulocyte macrophage colony-stimulating factor, anti-neutrophil cytoplasmic antibody, anti-Saccharomyces cerevisiae antibody, anti-laminaribioside carbohydrate IgG antibody, anti-mannobioside carbohydrate IgG antibody, antibody to the outer membrane protein of Escherichia coli, anti-CBir1) have been found to be present in patients with IBD and are potentially used in the diagnosis and prediction. The presence of these antibodies in the sera is due to the disruption of intestinal mucosa barrier and they may reflect a possibly genetic loss of immunological tolerance toward microbiota-derived antigens. Due to their non-invasive, easily accessible, repetitive and economical characteristics, these biomarkers have been found to serve as precious supplementary means in the diagnosis and disease evaluation of IBD. CONCLUSIONS: Currently, the most important utility of serological biomarkers is to evaluate the aggressive risks of disease phenotype, complications or surgery requirement, predict prognosis of the disease and distinguish CD from UC. However, they have limited values in making initially definite diagnosis for IBD. Therefore, more effective biomarkers with high sensitivity and specificity need to be further explored in the future.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Dissacarídeos/imunologia , Doenças Inflamatórias Intestinais/diagnóstico , Oligossacarídeos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Autoantígenos/imunologia , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/imunologia , Microbiota/imunologia
12.
Small ; 11(7): 871-6, 2015 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-25293504

RESUMO

Bulk (Ga1-x Zn x )(N1-x O x ) as a photocatalyst has received increasing attention as a potential solution for the energy shortage challenge; however, its catalytic performance is highly limited by its bulk form. To improve the photochemical potential, the nanoscale form of this multiple-metal oxynitrides is desirable. In this work, a new type of (Ga1-x Zn x )(N1-x O x ) nanostructure is obtained. Its composition can tuned to the full range (0.18 < x < 0.95). The (Ga1-x Zn x )(N1-x O x ) nanostructure exhibits excellent photocatalytic activity for overall water splitting, and the highest quantum efficiency of (Ga1-x Zn x )(N1-x O x ) is as high as 17.3% under visible light irradiation. Using this new type of (Ga1-x Zn x )(N1-x O x ) nanostructure, the narrowing of the bandgap for (Ga1-x Zn x )(N1-x O x ) is not only due to an increase in the valence band maximum, but it is also related to a decrease in the conduction band minimum.

13.
Phys Chem Chem Phys ; 17(26): 16705-8, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26058348

RESUMO

P-type sulphur-nitrogen (S-N) co-doped ZnO thin films are deposited and the effect of sulphur on the electrical properties is discussed. First-principles calculations indicate that the structure is most stable when the S atom is close to the N atom in the (0002) plane, implying that dual-doped ZnO is relatively feasible to approach. The partial density of states of S-N co-doped ZnO shows that the S impurity plays a vital role in forming the p-type conductivity.

14.
Mediators Inflamm ; 2015: 843089, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26106258

RESUMO

OBJECTIVES: Interactions between the host and gut microbial community contribute to the pathogenesis of Crohn's disease (CD). In this study, we aimed to detect lipopolysaccharide (LPS) and 1,3-ß-D-glucan (BG) in the sera of CD patients and clarify the potential role in the diagnosis and therapeutic approaches. MATERIALS AND METHODS: Serum samples were collected from 46 patients with active CD (A-CD), 22 CD patients at remission stage (R-CD), and 20 healthy controls, and the levels of LPS, BG, and TNF in sera were determined by ELISA. Moreover, sixteen patients with A-CD received anti-TNF monoclonal antibody therapy (infliximab, IFX) at a dose of 5 mg/kg body weight at weeks 0, 2, and 6, and the levels of LPS and BG were also tested at week 12 after the first intravenous infusion. RESULTS: Serum levels of LPS and BG were found to be markedly increased in A-CD patients compared with R-CD patients and healthy controls (P < 0.05). They were also observed to be positively correlated with CDAI, ESR, and SES-CD, respectively (P < 0.05). Furthermore, the levels of TNF in sera had a significant correlation with LPS and BG, respectively. The concentrations of LPS and BG were demonstrated to be significantly downregulated in the sera of A-CD patients 12 weeks after IFX treatment (P < 0.05), suggesting that blockade of TNF could inhibit bacterial endotoxin absorption, partially through improving intestinal mucosal barrier. CONCLUSIONS: Serum levels of LPS and BG are significantly increased in A-CD patients and positively correlated with the severity of the disease. Blockade of intestinal mucosal inflammation with IFX could reduce the levels of LPS and BG in sera. Therefore, this study has shed some light on measurement of serum LPS and BG in the diagnosis and treatment of CD patients.


Assuntos
Doença de Crohn/sangue , Lipopolissacarídeos/sangue , beta-Glucanas/sangue , Adolescente , Adulto , Criança , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
15.
Plants (Basel) ; 13(12)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38931090

RESUMO

Leaf nutrient resorption is a critical process in plant nutrient conservation during leaf senescence. However, the ecological mechanisms underlying the large variability in nitrogen (NRE) and phosphorous (PRE) resorption efficiencies among trees remain poorly understood. We conducted a comprehensive study on NRE and PRE variability using 61 tree individuals of 10 temperate broad-leaved tree species. Three potentially interrelated intrinsic ecological mechanisms (i.e., leaf senescence phenology, leaf pigments, and energy residual) were verified. We found that a delayed leaf senescence date, increased degradation of chlorophylls and carotenoids, biosynthesis of anthocyanins, and reduced nonstructural carbohydrates were all positively correlated with NRE and PRE at the individual tree level. The intrinsic factors affecting resorption efficiency were ranked in decreasing order of importance: leaf pigments > energy residual > senescence phenology. These factors explained more variability in NRE than in PRE. Our findings highlight the significance of these three ecological mechanisms in leaf nutrient resorption and have important implications for understanding how nutrient resorption responds to climate change.

16.
Mol Oncol ; 18(3): 580-605, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38060346

RESUMO

Homologous recombination (HR) repair for DNA double-strand breaks (DSBs) is critical for maintaining genome stability and conferring the resistance of tumor cells to chemotherapy. Nuclear PTEN which contains both phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and protein phosphatase plays a key role in HR repair, but the underlying mechanism remains largely elusive. We find that SUMOylated PTEN promotes HR repair but represses nonhomologous end joining (NHEJ) repair by directly dephosphorylating TP53-binding protein 1 (53BP1). During DNA damage responses (DDR), tumor suppressor ARF (p14ARF) was phosphorylated and then interacted efficiently with PTEN, thus promoting PTEN SUMOylation as an atypical SUMO E3 ligase. Interestingly, SUMOylated PTEN was subsequently recruited to the chromatin at DSB sites. This was because SUMO1 that was conjugated to PTEN was recognized and bound by the SUMO-interacting motif (SIM) of breast cancer type 1 susceptibility protein (BRCA1), which has been located to the core of 53BP1 foci on chromatin during S/G2 stage. Furthermore, these chromatin-loaded PTEN directly and specifically dephosphorylated phosphothreonine-543 (pT543) of 53BP1, resulting in the dissociation of the 53BP1 complex, which facilitated DNA end resection and ongoing HR repair. SUMOylation-site-mutated PTENK254R mice also showed decreased DNA damage repair in vivo. Blocking the PTEN SUMOylation pathway with either a SUMOylation inhibitor or a p14ARF(2-13) peptide sensitized tumor cells to chemotherapy. Our study therefore provides a new mechanistic understanding of PTEN in HR repair and clinical intervention of chemoresistant tumors.


Assuntos
Neoplasias , Proteína Supressora de Tumor p14ARF , Animais , Camundongos , Proteína BRCA1/genética , Cromatina , DNA/metabolismo , Dano ao DNA , Reparo do DNA por Junção de Extremidades , Reparo do DNA , Neoplasias/genética , Proteína Supressora de Tumor p14ARF/genética , Proteína Supressora de Tumor p14ARF/metabolismo
17.
Phys Chem Chem Phys ; 15(41): 17763-6, 2013 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-24068074

RESUMO

H was intentionally incorporated into as-deposited ZnO films by plasma exposure treatment. The resistivity of ZnO films was reduced to the order of 10(-3) Ω cm after H plasma treatment, and high conductive stability was identified using a post-annealing process. To find an explanation for the stable conductivity, first-principle calculation was performed. Results predicted that H atoms trapped in oxygen vacancies (V(O)) have the lowest formation energy. By reducing oxygen vacancies in as-deposited films by adding O2 into the working atmosphere, we further testified that H in V(O) is the origin of highly stable conductivity of ZnO films. Our study provided a solution to the problem of how to incorporate H into the V(O) position to produce highly stable H doped ZnO films.

18.
Biomimetics (Basel) ; 8(5)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37754169

RESUMO

A quick and effective way of segmenting images is the Otsu threshold method. However, the complexity of time grows exponentially as the number of thresolds rises. The aim of this study is to address the issues with the standard threshold image segmentation method's low segmentation effect and high time complexity. The two mutations differential evolution based on adaptive control parameters is presented, and the twofold mutation approach and adaptive control parameter search mechanism are used. Superior double-mutation differential evolution views Otsu threshold picture segmentation as an optimization issue, uses the maximum interclass variance technique as the objective function, determines the ideal threshold, and then implements multi-threshold image segmentation. The experimental findings demonstrate the robustness of the enhanced double-mutation differential evolution with adaptive control parameters. Compared to other benchmark algorithms, our algorithm excels in both image segmentation accuracy and time complexity, offering superior performance.

19.
RSC Adv ; 13(7): 4553-4563, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36760271

RESUMO

The encapsulation of fullerenes by carbon nanorings has gained increasing attention because of the unique molecular structure and special properties of the formed complexes. The host-guest interactions between the fullerenes and the carbon nanorings can influence the metal ion orientation and the molecular electronic structure. In this study, we hooped a series of carbide cluster metallofullerenes, namely Sc2C2@C2v(5)-C80, Sc2C2@C3v(8)-C82, and Sc2C2@D2d(23)-C84, with molecular carbon nanorings of [12]cycloparaphenylene ([12]CPP) and perfluoro[12]cycloparaphenylene (PF[12]CPP). The formed complexes were computationally studied via dispersion-corrected density functional theory calculations. The results showed that the deformation rate of PF[12]CPP after the formation of the fullerene-containing complexes was significantly smaller than that of [12]CPP. The binding energy and thermodynamic information showed that PF[12]CPP was more suitable for fullerene encapsulation. Moreover, charge population analysis showed that PF[12]CPP transferred more electrons to Sc2C2@C2n (n = 40, 41, and 42) compared with [12]CPP. Energy decomposition and real-space function analyses of host-guest interactions revealed the characteristics and nature of the noncovalent interactions in the supramolecules. These results provide theoretical support for the study of host-guest systems based on metallofullerenes.

20.
Oncogene ; 41(44): 4877-4892, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36192478

RESUMO

PTEN is frequently mutated in human cancers, which leads to the excessive activation of PI3K/AKT signaling and thus promotes tumorigenesis and drug resistance. Met1-linked ubiquitination (M1-Ubi) is also involved in cancer progression, but the mechanism is poorly defined. Here we find that HOIP, one important component of linear ubiquitin chain assembly complex (LUBAC), promotes prostate cancer (PCa) progression by enhancing AKT signaling in a PTEN-dependent manner. Mechanistically, PTEN is modified by M1-Ubi at two sites K144 and K197, which significantly inhibits PTEN phosphatase activity and thus accelerates PCa progression. More importantly, we identify that the high-frequency mutants PTENR173H and PTENR173C in PCa patients showed the enhanced level of M1-Ubi, which impairs PTEN function in inhibition of AKT phosphorylation and cell growth. We also find that HOIP depletion sensitizes PCa cells to therapeutic agents BKM120 and Enzalutamide. Furthermore, the clinical data analyses confirm that HOIP is upregulated and positively correlated with AKT activation in PCa patient specimen, which may promote PCa progression and increase the risk of PCa biochemical relapse. Together, our study reveals a key role of PTEN M1-Ubi in regulation of AKT activation and PCa progression, which may propose a new strategy for PCa therapy.


Assuntos
PTEN Fosfo-Hidrolase , Neoplasias da Próstata , Masculino , Humanos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Ubiquitinação
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