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1.
J Biol Chem ; 300(4): 107152, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462165

RESUMO

Prostate cancer is a leading cause of cancer-related mortality in males. Dysregulation of RNA adenine N-6 methylation (m6A) contributes to cancer malignancy. m6A on mRNA may affect mRNA splicing, turnover, transportation, and translation. m6A exerts these effects, at least partly, through dedicated m6A reader proteins, including YTH domain-containing family protein 2 (YTHDF2). YTHDF2 is necessary for development while its dysregulation is seen in various cancers, including prostate cancer. However, the mechanism underlying the dysregulation and function of YTHDF2 in cancer remains elusive. Here, we find that the deubiquitinase OUT domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) increases YTHDF2 protein stability by inhibiting its ubiquitination. With in vivo and in vitro ubiquitination assays, OTUB1 is shown to block ubiquitin transfer to YTHDF2 independent of its deubiquitinase activity. Furthermore, analysis of functional transcriptomic data and m6A-sequencing data identifies PRSS8 as a potential tumor suppressor gene. OTUB1 and YTHDF2 decrease mRNA and protein levels of PRSS8, which is a trypsin-like serine protease. Mechanistically, YTHDF2 binds PRSS8 mRNA and promotes its degradation in an m6A-dependent manner. Further functional study on cellular and mouse models reveals PRSS8 is a critical downstream effector of the OTUB1-YTHDF2 axis in prostate cancer. We find in prostate cancer cells, PRSS8 decreases nuclear ß-catenin level through E-cadherin, which is independent of its protease activity. Collectively, our study uncovers a key regulator of YTHDF2 protein stability and establishes a functional OTUB1-YTHDF2-PRSS8 axis in prostate cancer.


Assuntos
Proliferação de Células , Enzimas Desubiquitinantes , Neoplasias da Próstata , Proteínas de Ligação a RNA , Serina Endopeptidases , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Proliferação de Células/genética , Enzimas Desubiquitinantes/metabolismo , Enzimas Desubiquitinantes/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Estabilidade Proteica , Estabilidade de RNA/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Serina Endopeptidases/metabolismo , Ubiquitinação
2.
J Biol Chem ; 300(3): 105707, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309505

RESUMO

Liver cancer is notoriously refractory to conventional therapeutics. Tumor progression is governed by the interplay between tumor-promoting genes and tumor-suppressor genes. BRD4, an acetyl lysine-binding protein, is overexpressed in many cancer types, which promotes activation of a pro-tumor gene network. But the underlying mechanism for BRD4 overexpression remains incompletely understood. In addition, understanding the regulatory mechanism of BRD4 protein level will shed insight into BRD4-targeting therapeutics. In this study, we investigated the potential relation between BRD4 protein level and P53, the most frequently dysregulated tumor suppressor. By analyzing the TCGA datasets, we first identify a strong negative correlation between protein levels of P53 and BRD4 in liver cancer. Further investigation shows that P53 promotes BRD4 protein degradation. Mechanistically, P53 indirectly represses the transcription of USP1, a deubiquitinase, through the P21-RB1 axis. USP1 itself is also overexpressed in liver cancer and we show USP1 deubiquitinates BRD4 in vivo and in vitro, which increases BRD4 stability. With cell proliferation assays and xenograft model, we show the pro-tumor role of USP1 is partially mediated by BRD4. With functional transcriptomic analysis, we find the USP1-BRD4 axis upholds expression of a group of cancer-related genes. In summary, we identify a functional P53-P21-RB1-USP1-BRD4 axis in liver cancer.


Assuntos
Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular , Neoplasias Hepáticas , Proteínas Nucleares , Fatores de Transcrição , Proteases Específicas de Ubiquitina , Humanos , Proteínas que Contêm Bromodomínio/genética , Proteínas que Contêm Bromodomínio/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Genes Supressores de Tumor , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Ligação a Retinoblastoma/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteases Específicas de Ubiquitina/metabolismo
3.
J Biol Chem ; 300(5): 107270, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599381

RESUMO

Higher demand for nutrients including glucose is characteristic of cancer. "Starving cancer" has been pursued to curb tumor progression. An intriguing regime is to inhibit glucose transporter GLUT1 in cancer cells. In addition, during cancer progression, cancer cells may suffer from insufficient glucose supply. Yet, cancer cells can somehow tolerate glucose starvation. Uncovering the underlying mechanisms shall shed insight into cancer progression and benefit cancer therapy. TFE3 is a transcription factor known to activate autophagic genes. Physiological TFE3 activity is regulated by phosphorylation-triggered translocation responsive to nutrient status. We recently reported TFE3 constitutively localizes to the cell nucleus and promotes cell proliferation in kidney cancer even under nutrient replete condition. It remains unclear whether and how TFE3 responds to glucose starvation. In this study, we show TFE3 promotes kidney cancer cell resistance to glucose starvation by exposing cells to physiologically relevant glucose concentration. We find glucose starvation triggers TFE3 protein stabilization through increasing its O-GlcNAcylation. Furthermore, through an unbiased functional genomic study, we identify SLC36A1, a lysosomal amino acid transporter, as a TFE3 target gene sensitive to TFE3 protein level. We find SLC36A1 is overexpressed in kidney cancer, which promotes mTOR activity and kidney cancer cell proliferation. Importantly, SLC36A1 level is induced by glucose starvation through TFE3, which enhances cellular resistance to glucose starvation. Suppressing TFE3 or SLC36A1 significantly increases cellular sensitivity to GLUT1 inhibitor in kidney cancer cells. Collectively, we uncover a functional TFE3-SLC36A1 axis that responds to glucose starvation and enhances starvation tolerance in kidney cancer.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Glucose , Neoplasias Renais , Humanos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glucose/deficiência , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/genética , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Sistemas de Transporte de Aminoácidos , Simportadores
4.
J Biol Chem ; 299(5): 104621, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36935008

RESUMO

Autophagy plays a pivotal role in physiology and pathophysiology, including cancer. Mechanisms of autophagy dysregulation in cancer remain elusive. Loss of function of TRIM28, a multifunction protein, is seen in familial kidney malignancy, but the mechanism by which TRIM28 contributes to the etiology of kidney malignancy is unclear. In this study, we show TRIM28 retards kidney cancer cell proliferation through inhibiting autophagy. Mechanistically, we find TRIM28 promotes ubiquitination and proteasome-mediated degradation of transcription factor TFE3, which is critical for autophagic gene expression. Genetic activation of TFE3 due to gene fusion is known to cause human kidney malignancy, but whether and how transcription activation by TFE3 involves chromatin changes is unclear. Here, we find another mode of TFE3 activation in human renal carcinoma. We find that TFE3 is constitutively localized to the cell nucleus in human and mouse kidney cancer, where it increases autophagic gene expression and promotes cell autophagy as well as proliferation. We further uncover that TFE3 interacts with and recruits histone H3K27 demethylase KDM6A for autophagic gene upregulation. We reveal that KDM6A contributes to expression of TFE3 target genes through increasing H3K4me3 rather than demethylating H3K27. Collectively, in this study, we identify a functional TRIM28-TFE3-KDM6A signal axis, which plays a critical role in kidney cancer cell autophagy and proliferation.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Proteína 28 com Motivo Tripartido , Animais , Humanos , Camundongos , Autofagia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Carcinoma de Células Renais/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Histona Desmetilases/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteína 28 com Motivo Tripartido/genética , Proteína 28 com Motivo Tripartido/metabolismo
5.
Biomacromolecules ; 25(3): 1825-1837, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38336482

RESUMO

A synthetic biopolymer derived from furandicarboxylic acid monomer and hydroxyethyl-terminated poly(ether sulfone) is presented. The synthesis involves 4,4'-dichlorodiphenyl sulfone and 4,4-dihydroxydiphenyl sulfone, resulting in poly(butylene furandicarboxylate)-poly(ether sulfone) copolyesters (PBFES) through melt polycondensation with titanium-catalyzed polymerization. This facile method yields segmented polyesters incorporating polysulfone, creating a versatile group of high-temperature thermoplastics with adjustable thermomechanical properties. The PBFES copolyesters demonstrate an impressive tensile modulus of 2830 MPa and a tensile strength of 84 MPa for PBFES55. Additionally, the poly(ether sulfone) unit imparts a relatively high glass transition temperature (Tg), ranging from 36.6 °C for poly(butylene 2,5-furandicarboxylate) to 112.3 °C for PBFES62. Moreover, the complete amorphous film of PBFES exhibits excellent transparency and solvent resistance, making it suitable for applications, such as food packaging materials.


Assuntos
Alcenos , Materiais Biocompatíveis , Poliésteres , Polímeros , Sulfonas , Éteres
6.
Nanotechnology ; 35(15)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38176077

RESUMO

Aluminum-doped Ga2O3(AGO) thin films were prepared by plasma-enhanced atomic layer deposition (PE-ALD). The growth mechanism, surface morphology, chemical composition, and optical properties of AGO films were systematically investigated. The bandgap of AGO films can be theoretically set between 4.65 and 6.8 eV. Based on typical AGO films, metal-semiconductor-metal photodetectors (PDs) were created, and their photoelectric response was examined. The preliminary results show that PE-ALD grown AGO films have high quality and tunable bandgap, and AGO PDs possess superior characterizations to undoped films. The AGO realized using PE-ALD is expected to be an important route for the development of a new generation of gallium oxide-based photodetectors into the deep-ultraviolet.

7.
Cost Eff Resour Alloc ; 22(1): 38, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711056

RESUMO

BACKGROUND: Surgical staplers have been widely used to facilitate surgeries, and this study aimed to examine the real-world effectiveness of a new powered stapling system with Gripping Surface Technology (GST) on intraoperative outcomes of gastrectomy for gastric cancer. METHOD: The data were extracted from the Fourth Hospital of Hebei Medical University's (FHHMU) medical records system. Participants (N = 121 patients) were classified into the GST (n = 59) or non-GST group (n = 62), based on the use of the GST system. The intraoperative outcomes such as bleeding were assessed by reviewing video records. T-tests, Chi-square tests, and Mann-Whitney-U tests were used to compare the baseline characteristics between groups. Multivariate logistic regression was conducted for adjusting outcomes to study the effect of variables. RESULTS: Compared with the non-GST group, the GST group had significantly lower risks for intraoperative bleeding, intraoperative anastomosis intervention rate, intraoperative suture, and intraoperative pression (aORs: 0.0853 (p < 0.0001), 0.076 (p = 0.0003), 0.167 (p = 0.0012), and 0.221 (p = 0.0107), respectively). The GST group also consumed one fewer cartridge than the non-GST group (GST:5 vs non-GST: 6, p = 0.0241). CONCLUSION: The use of the GST system was associated with better intraoperative outcomes and lower cartridge consumption in Chinese real-world settings.

8.
BMC Anesthesiol ; 24(1): 231, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987679

RESUMO

BACKGROUND: Patients who are recovering from general anesthesia commonly exhibit symptoms such as dry lips, throat irritation, and thirst, prompting a desire to drink water in the post-anesthesia care unit (PACU). In this study, we aimed to evaluate the therapeutic effects and any potential complications of administering varying quantities of water to such patients. The primary objectives are to assess the safety and feasibility of early water intake after general anesthesia, specifically in the context of daytime surgery. METHODS: A total of 200 nongastrointestinal patients who underwent outpatient surgery were randomly assigned to four groups: Group A (drinking < 1 ml/kg), Group B (drinking 1-2 ml/kg), Group C (drinking > 2 ml/kg), and Group D (no water intake). We monitored changes in the assessment parameters before and after water consumption, as well as the incidence of post-drinking nausea and vomiting, and compared these outcomes among the four groups. RESULTS: Water intake led to a significant reduction in thirst, oropharyngeal discomfort, and pain scores and a notable increase in the gastric antrum motility index (MI), exhibiting statistical significance compared to the values before drinking (p < 0.05). Remarkably, higher water consumption correlated with enhanced gastrointestinal peristalsis. There was a significant difference in the antral MI among groups B, C, and A (p < 0.05). The occurrence of nausea and vomiting did not significantly differ among groups A, B, C, and D (p > 0.05). Early water consumption enhanced patient satisfaction with medical care, significantly varying from Group D (p < 0.05). CONCLUSION: Non-gastrointestinal surgical patients who passed pre-drinking water assessments post GA(general anesthesia)recovery could safely ingest moderate amounts of water in the PACU. Early water intake is both safe and feasible, effectively fostering swift postoperative recovery.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Período de Recuperação da Anestesia , Anestesia Geral , Água Potável , Estudos de Viabilidade , Humanos , Anestesia Geral/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Ambulatórios/métodos , Água Potável/administração & dosagem , Adulto , Ingestão de Líquidos , Náusea e Vômito Pós-Operatórios/epidemiologia , Sede/fisiologia , Idoso
9.
Sensors (Basel) ; 24(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38400465

RESUMO

Observing the vertical diffusion distribution of methane fugitive emissions from oil/gas facilities is significant for predicting the pollutant's spatiotemporal transport and quantifying the random emission sources. A method is proposed for methane's vertical distribution mapping by combining the laser path-integral sensing in non-non-cooperative open paths and the computer-assisted tomography (CAT) techniques. It uses a vertical-plume-mapping optical path configuration and adapts the developed dynamic relaxation and simultaneous algebraic reconstruction technique (DR-SART) into methane-emission-distribution reconstruction. A self-made miniaturized TDLAS telemetry sensor provides a reliable path to integral concentration information in non-non-cooperative open paths, with Allan variance analysis yielding a 3.59 ppm·m sensitivity. We employed a six-indexes system for the reconstruction performance analysis of four potential optical path-projection configurations and conducted the corresponding validation experiment. The results have shown that that of multiple fan-beams combined with parallel-beam modes (MFPM) is better than the other optical path-projection configurations, and its reconstruction similarity coefficient (ε) is at least 22.4% higher. For the different methane gas bag-layout schemes, the reconstruction errors of maximum concentration (γm) are consistently around 0.05, with the positional errors of maximum concentration (δ) falling within the range of 0.01 to 0.025. Moreover, considering the trade-off between scanning duration and reconstruction accuracy, it is recommended to appropriately extend the sensor measurement time on a single optical path to mitigate the impact of mechanical vibrations induced by scanning motion.

10.
Artigo em Inglês | MEDLINE | ID: mdl-39453340

RESUMO

INTRODUCTION: This study investigated the prevalence of maxillary transverse deficiency (MTD) in Chinese children and adolescents using revised Andrews' Element III analysis and studied transverse developmental characteristics of the maxillomandibular complex. METHODS: Plaster or digital casts of 794 participants aged 7-18 years were evaluated. MTD was diagnosed when the maxilla-mandible width difference, represented by the decompensated maxillary and mandibular first molars, exceeded 4 mm. RESULTS: The average prevalence of MTD among patients aged 7-18 years was 31.1%. Patients with MTD exhibited narrower maxillary and/or wider mandibular arches. Strikingly, 32.3% of participants with posterior crossbite because of local crowding or mandibular deviation were not diagnosed with MTD. Dental compensation, such as a greater buccolingual inclination of the first molars, was common in patients with MTD. Transverse growth of the maxillomandibular complex was completed by 17 years old, with the maxilla undergoing greater transverse growth than the mandible. The physiological buccolingual inclination of first molars was observed in patients without MTD. The 95% reference value of the palatal arch width was 31.9-42.3 mm. CONCLUSIONS: The prevalence of MTD is 31.1% among Chinese children and adolescents. However, it is often camouflaged by dental compensation and sagittal discrepancy. The etiology of MTD is uncoordinated width in the maxillomandibular complex, which is not solely attributed to a narrow maxilla but also to an excessively wide mandible. To enhance diagnostic accuracy, individualized measurements of the maxillomandibular complex and a revised dental decompensation formula, rather than posterior crossbite alone, are recommended for transverse diagnosis. A potential presence of MTD is indicated when the palatal arch width is <31.9 mm.

11.
J Biol Chem ; 298(9): 102374, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35970393

RESUMO

Advanced hepatocellular carcinoma (HCC) has a dismal prognosis. KDM1A (lysine demethylase 1A), overexpressed in multiple cancer types, is a lysine demethylase that targets both histone and nonhistone proteins. However, it is unclear how KDM1A expression affects HCC etiology. Here, we show that KDM1A can interact with and demethylate FKBP8 (FKBP prolyl isomerase 8), a cytoplasmic protein that regulates cell survival through the antiapoptotic protein BCL2 (B-cell lymphoma-2). We show that demethylation of FKBP8 enhances its ability to stabilize BCL2. Consistently, we observed positive correlation between KDM1A and BCL2 protein levels in liver cancer patients. Functionally, we reveal that FKBP8 demethylation by KDM1A is critical for liver cancer cell growth in vitro and in vivo. We went on to explore the mechanisms that might regulate KDM1A cytoplasmic localization. We found that the cytoplasmic localization and protein stability of KDM1A were promoted by acetylation at lysine-117 by the acetyl transferase KAT8 (lysine acetyltransferase 8). In agreement with this, we show that KDM1A-K117 (lysine 117) acetylation promotes demethylation of FKBP8 and level of BCL2. Finally, it has been shown that the efficacy of sorafenib, a first-line treatment for advanced HCC, is limited by clinical resistance. We show that KDM1A and BCL2 protein levels are increased during acquired sorafenib resistance, whereas inhibiting KDM1A can antagonize sorafenib resistance. Collectively, these results define a functional KDM1A-FKBP8-BCL2 axis in HCC.


Assuntos
Carcinoma Hepatocelular , Histona Desmetilases , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Lisina , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sorafenibe/farmacologia , Proteínas de Ligação a Tacrolimo/metabolismo
12.
Hum Genet ; 142(3): 445-456, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36658365

RESUMO

Single-nucleotide variants (SNVs) and copy number variations (CNVs) are the most common genomic variations that cause phenotypic diversity and genetic disorders. MALDI-TOF-MS is a rapid and cost-effective technique for multi-variant genotyping, but it is challenging to efficiently detect CNVs and clustered SNVs, especially to simultaneously detect CNVs and SNVs in one reaction. Herein, a novel strategy termed Target-Allele-Specific Probe Single-Base Extension (TASP-SBE) was devised to efficiently detect CNVs and clustered SNVs with MALDI-TOF-MS. By comprehensive use of traditional SBE and TASP-SBE strategies, a MALDI-TOF-MS assay was also developed to simultaneously detect 28 α-/ß-thalassemia mutations in a single reaction system, including 4 α-thalassemia deletions, 3 HBA and 21 HBB SNVs. The results showed that all 28 mutations were sensitively identified, and the CNVs of HBA/HBB genes were also accurately analyzed based on the ratio of peak height (RPH) between the target allele and reference gene. The double-blind evaluation results of 989 thalassemia carrier samples showed a 100% concordance of this assay with other methods. In conclusion, a one-tube MALDI-TOF-MS assay was developed to simultaneously genotype 28 thalassemia mutations. This novel TASP-SBE was also verified a practicable strategy for the detection of CNVs and clustered SNVs, providing a feasible approach for multi-variants analysis with MALDI-TOF-MS technique.


Assuntos
Talassemia , Talassemia beta , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Alelos , Talassemia beta/genética , Variações do Número de Cópias de DNA , Talassemia/genética , Mutação
13.
Opt Lett ; 48(9): 2305-2308, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37126260

RESUMO

We report a novel type of magnetically tunable diffractive optical element (DOE) based on ultrathin ferromagnetic (FM) Pt/Co stacks. The Pt/Co stacks are irradiated by Ar+ ions at selected areas so that the perpendicular anisotropy is spatially modulated and the DOEs can be tuned by an external magnetic field through the magnetooptical effect. Based on this concept, a diffraction grating and a Fresnel zone plate (FZP) were developed, and complementary experimental results corroborate that a magnetic field can simultaneously manipulate both the zeroth and the first diffraction orders of these DOEs. Importantly, this effect can be utilized to enhance or hide the image formed by the FZP. Our studies pave the way toward developing compact and high-precision DOEs with fast and robust tunability, facilitating various applications spanning a wide spectrum range.

14.
BMC Cancer ; 23(1): 536, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37308852

RESUMO

BACKGROUND: Lymph node size is considered as a criterion for possible lymph node metastasis in imageology. Micro lymph nodes are easily overlooked by surgeons and pathologists. This study investigated the influencing factors and prognosis of micro lymph node metastasis in gastric cancer. METHODS: 191 eligible gastric cancer patients who underwent D2 lymphadenectomy from June 2016 to June 2017 in the Third Surgery Department at the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Specimens were resected en bloc and the postoperative retrieval of micro lymph nodes was carried out by the operating surgeon for each lymph node station. Micro lymph nodes were submitted for pathological examination separately. According to the results of pathological results, patients were divided into the "micro-LNM (micro lymph node metastasis)" group (N = 85) and the "non micro-LNM" group (N = 106). RESULTS: The total number of lymph nodes retrieved was 10,954, of which 2998 (27.37%) were micro lymph nodes. A total of 85 (44.50%) gastric cancer patients had been proven to have micro lymph node metastasis. The mean number of micro lymph nodes retrieved was 15.7. The rate of micro lymph node metastasis was 8.1% (242/2998). Undifferentiated carcinoma (90.6% vs. 56.6%, P = 0.034) and more advanced Pathological N category (P < 0.001) were significantly related to micro lymph node metastasis. The patients with micro lymph node metastasis had a poor prognosis (HR for OS of 2.199, 95% CI = 1.335-3.622, P = 0.002). For the stage III patients, micro lymph node metastasis was associated with shorter 5-year OS (15.6% vs. 43.6%, P = 0.0004). CONCLUSIONS: Micro lymph node metastasis is an independent risk factor for poor prognosis in gastric cancer patients. Micro lymph node metastasis appears to be a supplement to N category in order to obtain more accurate pathological staging.


Assuntos
Carcinoma , Neoplasias Gástricas , Humanos , Metástase Linfática , Estudos Retrospectivos , Suplementos Nutricionais
15.
Inorg Chem ; 62(29): 11372-11380, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37431607

RESUMO

[n]Cycloparaphenylenes ([n]CPPs, n denotes the number of phenyl groups) are difficult to synthesize because of the strain related to their bent phenyl rings. In particular, the strain in [3]CPP is high enough to destroy the π electron delocalization, leading to the spontaneous structural transition to an energetically more stable "bond-shift" (BS) isomer ([3]BS). In this contribution, we propose to achieve [3]CPP by enhancing the π electron delocalization through hosting a guest metal atom. Our computations revealed that Sc could stabilize [3]CPP by forming the [Sc©[3]CPP]+ complex through the favorable π-Sc donation-backdonation interactions. Thermodynamically, the binding energy between the Sc atom and [3]CPP was -205.7 kcal/mol, which could well compensate not only the energy difference of 44.2 kcal/mol between [3]CPP and [3]BS but also the extremely high strain energy of 170.3 kcal/mol in [3]CPP. Simultaneously, the [Sc©[3]CPP]+ complex is stable up to 1500 K in dynamic simulations, suggesting its high viability in the synthesis.

16.
Artigo em Inglês | MEDLINE | ID: mdl-37944981

RESUMO

Objective: Investigating the therapeutic effect of the non-cutting traction seton technique on perianal abscess. Methods: The clinical data of 70 patients with perianal abscesses diagnosed and treated by the Department of Anorectal Surgery of University Affiliated Hospital from January 2020 to December 2021 were collected, and conducted a retrospective study on them, of which 40 cases were treated with non-cut traction seton in the study group, and other 30 cases were treated with perianal abscess incision and drainage in the control group. The perioperative indexes (operation time, intraoperative bleeding volume, time of postoperative dressing change, time of postoperative granulation tissue formation, postoperative defecation-control ability, postoperative pain score, postoperative wound cleanliness) and follow-up indexes (wound healing time, incontinence Wexner score, recurrence rate, patient satisfaction) were compared between these two groups. Results: The operation time of the study group was more than that of the control group, and the difference was not statistically significant (P > .05). The intraoperative bleeding volume, time of postoperative dressing change, time of postoperative granulation tissue formation, the scores on postoperative defecation-control ability, the scores on postoperative wound cleanliness, postoperative complication rate, postoperative pain score, time of wound healing, incontinence Wexner score, and recurrence rate all from the study group were better than those in the control group. The patient satisfaction from the study group was higher than that in the control group, and the above differences were statistically significant (P < .05). Conclusion: Non-cutting traction suture technique has obvious advantages in the treatment of perianal abscess, shortening wound healing time and granulation tissue formation time, reducing intraoperative blood loss and postoperative complication rate, etc. It provides a reference for clinical treatment of perianal abscess.

17.
Bioorg Med Chem Lett ; 70: 128802, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35598792

RESUMO

In order to acquire both expanded binding ability with the EphA2 receptor and superior drug delivery capacity, we designed and synthesized the modified GO-SWL-Ahx-K-SWL conjugate as a potential targeted therapeutic drug for non-small cell lung cancer (NSCLC). Various characterization methods have confirmed that the conjugate is consistent with the theoretical peptide. The cytotoxicity test results showed that the conjugate was slightly more toxic to A549 cells than in 3 T3 cells, and the toxicity increased in a concentration-dependent manner. Single photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging was performed to evaluate the conjugate binding to EphA2 receptor in vivo. The images showed obvious radioactive concentration in tumor tissues and significantly higher ratios of the tumor and muscle in the 125I-GO-SWL-Ahx-K-SWL group (10.78) than in the 125I-SWL-Ahx-K-SWL group (5.21) at all three time points (P < 0.01).


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Receptor EphA2 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Peptídeos/química , Receptor EphA2/metabolismo
18.
Nanotechnology ; 33(25)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35299168

RESUMO

Stretchable strain sensor, an important paradigm of wearable sensor which can be attached onto clothing or even human skin, is widely used in healthcare, human motion monitoring and human-machine interaction. Pattern-available and facile manufacturing process for strain sensor is pursued all the time. A carbon nanotube (CNT)/silver nanowire (AgNW)-based stretchable strain sensor fabricated by a facile process is reported here. The strain sensor exhibits a considerable Gauge factor of 6.7, long-term durability (>1000 stretching cycles), fast response and recovery (420 ms and 600 ms, respectively), hence the sensor can fulfill the measurement of finger movement. Accordingly, a smart glove comprising a sensor array and a flexible printed circuit board is assembled to detect the bending movement of five fingers simultaneously. Moreover, the glove is wireless and basically fully flexible, it can detect the finger bending of wearer and display the responses distinctly on an APP of a smart phone or a host computer. Our strain senor and smart glove will broaden the materials and applications of wearable sensors.


Assuntos
Nanotubos de Carbono , Nanofios , Dispositivos Eletrônicos Vestíveis , Humanos , Movimento , Prata
19.
Dig Dis Sci ; 67(4): 1260-1270, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33811565

RESUMO

BACKGROUND: Colorectal cancer is commonly malignant tumor. Herein, we demonstrate that pseudouridylate synthase 7 (PUS7) is closely related to colon cancer. But the biological role of PUS7 in colon cancer is not known. AIMS: The present study aims to investigate the effects of PUS7 in colon cancer clinical samples and cells and the related molecular mechanism. METHODS: A profile data set was downloaded from the Cancer Genome Atlas database, which included data from colon cancer tissue samples and normal tissue samples. The top 200 differentially expressed genes were subsequently investigated by a protein-protein interaction (PPI) network. RT-PCR and western blot assays were used to determine gene expression levels. CCK8 assay, colony formation experiment, transwell and flow cytometry assay were used to determine cell viability, proliferation, invasion, and apoptosis, respectively. RESULTS: PUS7 is a key gene from the most significant module of the PPI network. PUS7 was upregulated in colon cancer tissues and cell lines. Moreover, PUS7 overexpression is significantly related to the poor survival rate for 60 colon cancer's patients. Cell proliferation and invasion was significantly reduced by PUS7 inhibition and promoted by PUS7 overexpression. The protein levels of cleaved caspase-3/9, c-myc, E-cadherin and vimentin genes were significantly regulated in colon cancer cells transfected with PUS7 interference or overexpression. PUS7 overexpression significantly upregulated the phosphorylation levels of PI3K, AKT and mTOR. CONCLUSION: The results of this study demonstrate that PUS7 overexpression upregulates cell proliferation, invasion and inhibits cell apoptosis of colon cancer cells via activating PI3K/AKT/mTOR signaling pathway.


Assuntos
Neoplasias do Colo , Transferases Intramoleculares/metabolismo , Proteínas Proto-Oncogênicas c-akt , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
20.
Surg Endosc ; 36(5): 3209-3216, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34254184

RESUMO

BACKGROUND: There is a lack of comparative analyses on the use of carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) tracer technology for lymph node detection and their perioperative safety in robotic radical gastrectomy. METHODS: A retrospective analysis was performed on patients who underwent robotic distal gastrectomy between November 2019 and November 2020. Patients were assigned to the CNSI group, the ICG group, or the control group. The number of lymph nodes detected, number of lymph nodes detected at each station, number of micro lymph nodes detected, rate of lymph node metastasis, and inoperative and postoperative recovery were compared. RESULTS: Of the 93 patients analyzed, 34 were in the CNSI group, 27 were in the ICG group, and 32 were in the control group. The mean number of lymph nodes retrieved in the CNSI group (48.44) was higher than that in the ICG (39.19) and control (35.28) groups (P = 0.004; P < 0.001), and there was no difference between the ICG and control groups (P = 0.102). The mean number of micro lymph nodes retrieved in the CNSI group (13.24) was higher than that in the ICG (5.74) and control (5.66) groups (P < 0.001). The lymph node metastasis rates in the CNSI, ICG, and control groups were 5.03, 4.63, and 5.93%, respectively (P > 0.05). CONCLUSION: The effect of CNSI on lymph node dissection and sorting was better than that of ICG, and CNSI improved the surgical quality and reduced lymph node staging deviation to a greater extent. CNSI was better than ICG in terms of improving the number of micro lymph nodes detected.


Assuntos
Nanopartículas , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Carbono , Gastrectomia , Humanos , Verde de Indocianina , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
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