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1.
Hum Cell ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35545731

RESUMO

Serum-derived extracellular vesicles (EVs) containing non-coding RNAs have been indicated to serve as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma (LSCC), while their functional role remains to be explored. Here, we summarize the possible mechanism explaining the laryngeal carcinogenesis and the associated changes with the involvement of extracellular microRNA (miR)-27a from serum of LSCC patients. Serum-derived EVs from LSCC patients were found to increase the proliferative activity and decreased the apoptotic activity of LSCC cells. miRNA microarrays revealed that miR-27a expression was elevated after EV treatment. miR-27a expression was elevated in LSCC tissues and predicted a poor prognosis for patients. Downregulation of miR-27a inhibited the effect of EVs to reduce the activity of LSCC cells in vitro and to suppress tumor development in vivo. miR-27a targeted SMAD family member 4 (Smad4) to mediate the Wnt/ß-catenin pathway, which was induced under the influence of EVs. Smad4 was downregulated in LSCC tissues, and simultaneous overexpression of miR-27a and Smad4 resulted in reduced cell activity and tumorigenicity. In conclusion, serum-derived EVs support the laryngeal carcinogenesis at least partially via transferring miR-27a. miR-27a targets Smad4 and is a biomarker to predict LSCC prognosis.

2.
Adv Sci (Weinh) ; : e2200590, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35470581

RESUMO

HgTe film is widely used for quantum Hall well studies and devices, as it has unique properties, like band gap inversion, carrier-type switch, and topological evolution depending on the film thickness modulation near the so-called critical thickness (63.5 Å), while its counterpart bulk materials do not hold these nontrivial properties at ambient pressure. Here, much richer transport properties emerging in bulk HgTe crystal through pressure-tuning are reported. Not only the above-mentioned abnormal properties can be realized in a 400 nm thick bulk HgTe single crystal, but superconductivity is also discovered in a series of high-pressure phases. Combining crystal structure, electrical transport, and Hall coefficient measurements, a p-n carrier type switching is observed in the first high-pressure cinnabar phase. Superconductivity emerges after the semiconductor-to-metal transition at 3.9 GPa and persists up to 54 GPa, crossing four high-pressure phases with an increased upper critical field. Density functional theory calculations confirm that a surface-dominated topologic band structure contributes these exotic properties under high pressure. This discovery presents broad and efficient tuning effects by pressure on the lattice structure and electronic modulations compared to the thickness-dependent critical properties in 2D and 3D topologic insulators and semimetals.

3.
Environ Sci Pollut Res Int ; 29(3): 3498-3509, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34389950

RESUMO

This study examined the effects of Stmn2 on phenotype transformation of vascular smooth muscle in vascular injury via RNA sequencing and experimental validation. Total RNA was extracted for RNA sequencing after 1, 3 and 5 days of injury to screen the differentially expressed genes (DEGs). Western blot was used to detect the protein expression of Stmn2 and its associated targets. The morphological changes of carotid arteries in rats were examined by hematoxylin and eosin (H&E) staining. The expression of vascular smooth muscle cell (VSMC) phenotype markers smooth muscle alpha-actin (α-SMA), vimentin and OPN were detected by immunohistochemistry. DEGs were related to the extracellular matrix and other cell components outside the plasma membrane. They were associated with protein binding, cytoskeleton protein binding, signal receptor binding and other molecular functions, actin cytoskeleton regulation and other Kyoto Encyclopedia of Genes and Genomes pathways. Stmn2 was identified as the hub gene of actin cytoskeleton pathway and vascular disease, and its expression followed the trend of decreasing initially and increasing afterwards during the progress of vascular injury. Western blot assay showed that the expression of Stmn2 and Tubulin decreased immediately after vascular injury; Stmn2 overexpression significantly up-regulated the expression of osteopontin and α-SMA and vimentin in VSMCs. The results of morphology analysis and immunostaining also showed that Stmn2 overexpression promoted the intima thickening and enhanced the proliferating cell nuclear antigen expression in the injured vascular tissues. In conclusion, our results implied that Stmn2 may play a potential role in vascular injury, which may be associated with VSMC phenotype transformation. Further studies are warranted to determine detailed molecular mechanisms of Stmn2 in vascular injury.


Assuntos
Músculo Liso Vascular , Lesões do Sistema Vascular , Animais , Movimento Celular , Proliferação de Células , Células Cultivadas , Fenótipo , Ratos , Análise de Sequência de RNA , Lesões do Sistema Vascular/genética
4.
Small ; 18(12): e2105989, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35088522

RESUMO

Biomedical imaging technology (like digital subtraction angiography (DSA)) based on contrast agents has been widely employed in the diagnosis of vascular-related diseases. While the DSA achieves the high-resolution observation of specified vessels and their downstream perfusion at the cost of invasive, radioactive operation and hepatorenal toxicity. To address those problems, this study develops arterial labeling ultrasound (US) subtraction angiography (ALUSA) based on a new perfluorobutane (PFB) nanodroplets with a lower vaporization threshold through spontaneous nucleation. The nanodroplets can be selectively vaporized to microbubbles, indicating a highly echogenic signal at B-mode images only using a diagnostic transducer. By labeling a single blood vessel for nanodroplets vaporization and tracking its downstream blood perfusion in segmental renal arteries at a frame rate of 500 Hz. The results demonstrate the color-coded super-resolution ALUSA image, exhibiting the downstream arcuate and interlobular arteries of each segmental renal artery with a resolution of 36 µm in a rabbit kidney. Furthermore, ALUSA could offer the vascular structures, blood flow velocity, and direction of their primary supply vessels in the mouse breast tumor. ALUSA fills the gap of noninvasive labeling angiography in US and opens a broad vista in the diagnosis and treatment of tumor and vascular-related diseases.


Assuntos
Acústica , Microbolhas , Angiografia Digital , Animais , Artérias , Camundongos , Coelhos , Ultrassonografia/métodos
5.
ACS Nano ; 15(10): 16913-16923, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34647449

RESUMO

The advent of localization-based super-resolution ultrasound (SRUS) imaging creates a vista for precision vasculature and hemodynamic measurements in brain science, cardiovascular diseases, and cancer. As blinking fluorophores are crucial to super-resolution optical imaging, blinking acoustic contrast agents enabling ultrasound localization microscopy have been highly sought, but only with limited success. Here we report on the discovery and characterization of a type of blinking acoustic nanodroplets (BANDs) ideal for SRUS. BANDs of 200-500 nm diameters comprise a perfluorocarbon-filled core and a shell of DSPC, Pluronic F68, and DSPE-PEG2000. When driven by clinically safe acoustic pulses (MI < 1.9) provided by a diagnostic ultrasound transducer, BANDs underwent reversible vaporization and reliquefaction, manifesting as "blinks", at rates of up to 5 kHz. By sparse activation of perfluorohexane-filled BANDs-C6 at high concentrations, only 100 frames of ultrasound imaging were sufficient to reconstruct super-resolution images of a no-flow tube through either cumulative localization or temporal radiality autocorrelation. Furthermore, the use of high-density BANDs-C6-4 (1 × 108/mL) with a 1:9 admixture of perfluorohexane and perfluorobutane supported the fast SRUS imaging of muscle vasculature in live animals, at 64 µm resolution requiring only 100 frames per layer. We anticipate that the BANDs developed here will greatly boost the application of SRUS in both basic science and clinical settings.


Assuntos
Piscadela , Meios de Contraste , Acústica , Animais , Imagem Óptica , Ultrassonografia
6.
Bioengineered ; 12(1): 5220-5230, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34455918

RESUMO

Abnormal expression of circular RNA (circRNA) is closely related to the occurrence and development of many cancers. By screening the expression of circRNA, we identified a novel circRNA termed as has_circ_0023326 in laryngeal squamous cell carcinoma (LSCC). We verified the expression of circPPFIA1 and found that it was upregulated in LSCC tissues compared to the adjacent normal tissues. Functional studies were carried out to detect the effect of circPPFIA1 expression on the phenotype of LSCC cells. These results suggest that circPPFIA1 knockdown can suppress the proliferation, migration, and invasion of LSCC cells, while circPPFIA1 overexpression can promote these processes. Mechanistically, miR-340-3p was predicted to be the target miRNA sponged by circPPFIA1 as confirmed through the luciferase assay and rescue experiments. In addition, miR-340-3p was found to target ELK1 and inhibit its expression. Taken together, circPPFIA1 promotes the progression of LSCC via the miR-340-3p/ELK1 signaling axis, which may serve as a novel prognostic or therapeutic target for LSCC.


Assuntos
Neoplasias Laríngeas/genética , MicroRNAs/genética , RNA Circular/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Proteínas Elk-1 do Domínio ets/genética , Animais , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Camundongos , MicroRNAs/metabolismo , RNA Circular/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Proteínas Elk-1 do Domínio ets/metabolismo
7.
Diabetes Res Clin Pract ; 177: 108786, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33812901

RESUMO

AIMS: The triglyceride glucose (TyG) index is a marker of insulin resistance. However, the prognostic value thereof in patients with chronic heart failure (CHF) and type 2 diabetes remains unclear. METHODS: This study included patients diagnosed with CHF and type 2 diabetes in Fuwai Hospital of Chinese Academy of Medical Sciences, Shenzhen, from January 2017 to July 2019. The primary endpoint was cardiovascular death or rehospitalization for heart failure. RESULTS: The study included 546 patients with CHF and type 2 diabetes. We divided the patients into three groups (T1 [TyG index < 8.55], T2 [TyG index ≥ 8.55 and < 9.06], and T3 [TyG index ≥ 9.06]) according to the TyG index level. The incidence of the primary outcome in the T3 group was significantly higher than that in the T1 group. There was no significant difference between the T1 and T2 groups. The trend test revealed a positive correlation between the TyG index and the incidence of the primary outcome (P = 0.001). CONCLUSIONS: There is a positive correlation between the TyG index and the prognosis of patients with CHF and type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Glicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Glucose , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Triglicerídeos
8.
Ann Transl Med ; 9(2): 118, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33569420

RESUMO

BACKGROUND: Previous studies have shown that the lactate/albumin (L/A) ratio plays a role in predicting the outcomes of septic shock or severe sepsis. However, the role of the L/A ratio in predicting the outcomes of critically ill patients with heart failure remains unclear. We therefore performed a retrospective study to clarify this issue. METHODS: The study was based on the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database and included critically ill adult patients with heart failure. The primary endpoints were 28-day and 1-year all-cause mortality after admission at the intensive care unit. RESULTS: We analyzed 4,562 patients in this study. We divided the participants into five groups according to the L/A ratio: quintile (Q)1 (L/A ratio ≤0.40, n=913), Q2 (0.40< L/A ratio ≤0.51, n=912), Q3 (0.51< L/A ratio ≤0.66, n=912), Q4 (0.66< L/A ratio ≤0.92, n=912), and Q5 (L/A ratio >0.92, n=913). After stratifying by L/A ratio, the risk of 28-day and 1-year mortality were significantly different between the groups (log-rank P<0.001). Compared with the first quintile, the second, third, fourth, and fifth quintiles of the L/A ratio were associated with higher 28-day [hazard ratio (HR) 1.57, 95% confidence interval (CI): 1.21-2.03 for Q3, HR 1.72, 95% CI: 1.34-2.21 for Q4, and HR 3.15, 95% CI: 2.47-4.01 for Q5) and 1-year mortality (HR 1.19, 95% CI: 1.00-1.41 for Q2, HR 1.36, 95% CI: 1.15-1.60 for Q3, HR 1.42, 95% CI: 1.20-1.67 for Q4, and HR 2.46, 95% CI: 2.09-2.89 for Q5). The restricted cubic spline showed that the L/A ratio positively correlated with both 28-day and 1-year all-cause mortality. CONCLUSIONS: The L/A ratio could serve as a predictor of short and long-term mortality in critically ill patients with heart failure.

9.
J Recept Signal Transduct Res ; 41(1): 6-14, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32605511

RESUMO

Acute myocardial infarction (AMI) represents a severe coronary heart disease with relatively high rate of mortality and usually can lead to the damage of the myocardial tissues. Reperfusion of the ischemic myocardial tissues can minimize AMI-induced damage. As far as we know, the molecular mechanisms underlying ischemia/reperfusion (I/R)-induced injury remains elusive. This study was undertaken to explore the role of miR-1247-3p in regulating myocardial I/R injury. The hypoxia/reoxygenation (H/R)-treated H9c2 cells showed a decreased cell viability and mitochondrial membrane potential with an increase in the apoptosis; furthermore, miR-1247-3p was down-regulated in these cells. MiR-1247-3p overexpression attenuated H/R-induced H9c2 cell injury; while miR-1247-3p knockdown in H9c2 cells exhibited similar effects being observed in H/R-treated cells. The bioinformatics prediction revealed Bcl-2-like protein 11 (BCL2L11) and caspase-2 were two potential targets for miR-1247-3p, and functional assays confirmed that miR-1247-3p targeted both BCL2L11 and caspase-2 3' untranslated regions, which lead to the repressed expression of these genes. Silencing of BCL2L11 and caspase-2 both, respectively, counteracted the H9c2 cell injury caused by H/R treatment. Moreover, BCL2L11 and caspase-2 overexpression, respectively, impaired the protective effects of miR-1247-3p overexpression on H/R-treated H9c2 cells. The data in the present investigation revealed that miR-1247-3p restoration exhibited protective effects on H/R-induced cardiomyocyte injury through targeting BCL2L11 and caspase-2, implying that miR-1247-3p along with caspase-2/BCL2L11 signaling may provide novel sight for a better understating of I/R-induced myocardial damage. The role of miR-1247-3p might be further confirmed in animal models and clinical studies.


Assuntos
Proteína 11 Semelhante a Bcl-2/genética , Caspase 2/genética , MicroRNAs/genética , Miocárdio/metabolismo , Traumatismo por Reperfusão/genética , Animais , Apoptose/genética , Hipóxia Celular/genética , Sobrevivência Celular/genética , Regulação da Expressão Gênica/genética , Humanos , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Substâncias Protetoras/farmacologia , Ratos , Traumatismo por Reperfusão/patologia , Transdução de Sinais/genética
10.
ESC Heart Fail ; 8(1): 250-258, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33314789

RESUMO

AIMS: The relationship between baseline base excess (BE) and survival outcomes in patients with congestive heart failure (CHF) is unclear. Therefore, we aimed to investigate this relationship based on the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database (v1.4). METHODS AND RESULTS: This retrospective cohort study included 5956 adult patients with CHF from the MIMIC-III database from 2001 to 2012. Using the Cox proportional-hazard analysis and Kaplan-Meier plot, we evaluated the relationship between baseline BE and all-cause death at 1 year after admission to the intensive care unit. At the 1 year follow-up, 2104 participants (35.3%) had died. There was an association between BE and all-cause death (log-rank test P < 0.0001). In the Cox regression model adjusted for demographic and clinical variables, the risk of all-cause death in the first (BE ≤ -8), second (-8 < BE ≤ -3), fourth (2 < BE ≤ 7), and fifth (BE > 7) BE groups was significantly higher than that in the third BE group (-3 < BE ≤ 2) [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.62-2.43, HR 1.40, 95% CI 1.23-1.60, HR 1.46, 95% CI 1.26-1.69, and HR 1.68, 95% 1.33-2.12, respectively]. Similar results were observed when BE was modelled as a continuous variable using a Cox regression model with a restricted cubic spline. CONCLUSIONS: This study demonstrated the existence of a U-shaped relationship between BE and survival outcome in patients with CHF. Both low and high BE increased the risk of all-cause mortality.


Assuntos
Insuficiência Cardíaca , Adulto , Hospitalização , Humanos , Unidades de Terapia Intensiva , Modelos de Riscos Proporcionais , Estudos Retrospectivos
11.
Nanotechnology ; 31(50): 505710, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-32906092

RESUMO

We have successfully fabricated Ti-based MXenes flakes, Ti3C2Tx, by chemical etching, then prepared it as an organic dispersion and finally spin-coated it on polyimide plastic substrate for terahertz wave shielding. The shielding effectivity of the 12 µm ultra-thin film can reach up to 17 dB measured by the terahertz time-domain spectra. We can attribute the excellent phenomenon to the intrinsic absorption of triple-layered Ti3C2, due to the similar double-peak type refraction curves, which have been respectively observed from the experimental samples and the simulation ones. High conductivity and strong THz absorption indicate the Ti3C2Tx MXene is the absorptive electromagnetic shielding material. Comparing with other kinds of THz shielding materials, the Ti-based MXenes might be a potential candidate for the next generation of ultra-thin and lightweight THz shielding.

12.
World J Surg Oncol ; 18(1): 90, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375789

RESUMO

BACKGROUND: Maxillary sinus squamous cell carcinoma (MSSCC) is a relatively rare head and neck cancer with poorly defined prognosis, and the present study aimed to investigate the outcomes for MSSCC according to different treatments. METHODS: Tianjin Medical University Cancer Institute and Hospital pathology database was reviewed from 2007 to 2017, and 98 patients with pathologically confirmed MSSCC were enrolled. Retrospective analysis and follow-up were performed for each patient. Multivariate analysis of prognostic factors was performed using Cox's regression model. RESULTS: For all the 98 cases of MSSCC, the 5-year overall survival (OS) and disease-free survival (DFS) rates were 31.0% and 29.3%, respectively. Among 98 patient, 33 patients were treated with systemic treatment (NON-SUR), 19 patients underwent neoadjuvant chemotherapy and/or radiotherapy followed by surgery (CT/RT+SUR), 38 patients received surgery followed by chemotherapy and/or radiotherapy (SUR+RT/CT), and 8 patients were performed surgery alone (SUR).The OS rate for each group was 27.3%, 57.9%, 30.6% and 37.5%, respectively, while the DFS was 21.2%, 36.8%, 31.6% and 25.0%, respectively. The OS rate of CT/RT+SUR was significantly higher than that of NON-SUR and SUR+CT/RT groups (P < 0.05). Multivariate analysis revealed that smoking, low differentiation, and advanced T stage were independent risk factors for OS, while low differentiation and advanced N stage for DFS. CONCLUSIONS: Surgery-based treatment is still the first-line therapeutic strategy for MSSCC. And neoadjuvant chemoradiotherapy followed by surgery is highly recommended for MSSCC patients, especially those with advanced tumors or requesting high quality of life.


Assuntos
Quimiorradioterapia Adjuvante/estatística & dados numéricos , Neoplasias do Seio Maxilar/terapia , Procedimentos Cirúrgicos Nasais/estatística & dados numéricos , Terapia Neoadjuvante/estatística & dados numéricos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Seio Maxilar/patologia , Seio Maxilar/cirurgia , Neoplasias do Seio Maxilar/mortalidade , Neoplasias do Seio Maxilar/patologia , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Nasais/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Prognóstico , Qualidade de Vida , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto Jovem
13.
Phys Chem Chem Phys ; 22(9): 4946-4956, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32073069

RESUMO

The structural, mechanical and electronic properties of the MoSSe/WSSe van der Waals (vdW) heterostructure under various degrees of horizontal and vertical strain are systematically investigated based on first-principles methods. It is found that the MoSSe/WSSe vdW heterostructure of the most stable AB stacking is a direct band gap semiconductor and exhibits a type-II band alignment, which demonstrates an effective separation of photogenerated electron-hole pairs and increases their lifetime accordingly. The high angle-dependent Young's modulus and normal Poisson's ratios show the mechanical stability and anisotropy. It is found that the band gap of the heterostructure can be modulated effectively by applying strain, exhibiting a decreasing trend with increasing strain, and even lead to an intriguing semiconductor-metal transition under a certain large tensile strain. In particular, a negative correlation between the band gap and structure pressure provides a theoretical basis for experimentally regulating the electronic properties. Moreover, different strains can induce two different conditions of direct-indirect transition or can maintain the characteristics of the direct-band-gap. All these interesting results provide a detailed understanding of the MoSSe/WSSe vdW heterostructure under strain and indicate that it is a good candidate for low-dimensional electronic, nano-electronic and optoelectronic devices.

14.
Arch Med Sci ; 15(4): 837-844, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31360178

RESUMO

Introduction: The aim of the study was to evaluate the effects of cytochrome P450 2C19*2 (CYP2C19*2) on ischemic and bleeding events in the Chinese Han population. Material and methods: Patients after coronary artery stenting were enrolled for genotyping CYP2C19*2. Platelet reactivity 4 weeks after stent implantation was compared between different genotype groups. Ischemic and bleeding events were compared after 6 months' follow-up. Results: A total of 255 patients were enrolled and 57.7% and 42.3% of patients presented with stable angina and acute coronary syndrome, respectively. The prevalence of homozygous (AA) and heterozygous (GA) CYP2C19*2 variants was 3.5% and 24.7% respectively, and the prevalence of wild type (GG) was 71.8%. Compared to GG and GA genotype groups, the absolute platelet activity reduction was significantly lower in AA genotype (GG 43.6 ±7.8%, GA 31.9 ±6.5%, and AA 24.8 ±5.3%, p < 0.01 for trend). After 6 months' follow-up, 3.3%, 4.8% and 11.1% of patients experienced ischemic events in GG, GA and AA genotype groups, respectively (p = 0.003 for trend). After adjusting for traditional risk factors, AA genotype was significantly associated with ischemic events, with hazard ratio 1.19 and 95% confidence interval 1.08-1.30 (p = 0.013). Also, 2.2%, 1.6% and 0% of patients experienced bleeding events in GG, GA and AA genotype groups (p = 0.153 for trend). No independent association of CYP2C19*2 genotype and bleeding events was observed. Conclusions: Genotyping of CYP2C19*2 may be useful to guide antiplatelet treatment in the Chinese Han population. Randomized controlled trials are warranted to investigate whether genotype-guided antiplatelet treatment could reduce ischemic events.

15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(7): 731-733, 2019 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-31302923

RESUMO

OBJECTIVE: To report on a novel weak D type identified in a Chinese individual. METHODS: Peripheral blood sample was collected for a voluntary blood donor with weakened expression of D antigen. Routine serological testing was carried out to determine the D, C, c, E and e antigens of the Rh blood group. A D-screening kit was used to analyze the RhD epitopes. The 10 exons and flanking intronic regions of the RHD gene were sequenced. The zygosity of RHD was determined with a sequence-specific primer PCR method. RESULTS: A novel RHD allele, RHD (1022T>A), was found in the subject with a weak D phenotype. Serological testing of the RhD epitopes has coined with the weak D phenotype. CONCLUSION: A novel weak D allele has been identified in Chinese population.


Assuntos
Alelos , Sistema do Grupo Sanguíneo Rh-Hr/genética , China , Éxons , Genótipo , Humanos , Íntrons
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(6): 636-638, 2019 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-31055825

RESUMO

OBJECTIVE: To explore the molecular basis for an individual with para-Bombay phenotype of the H blood group. METHODS: Intron 5 to 3'-UTR of the ABO gene and exon 4 of the FUT1 gene were amplified with PCR and subjected to direct sequencing. Mutations of the FUT1 gene were identified by TOPO cloning sequencing. RESULTS: Direct sequencing showed that her ABO genotype was B101/O01. TOPO cloning sequencing found that this individual had three mutations of the FUT1 gene, including an heterozygous AG deletion (CAGAGAG→CAGAG) at position 547 to 552, and two C→T mutations at positions 35 (C35T) and 293 (C293T) on the other homologous chromosome. The two alleles comprised a new recombination of mutations c.35T>C and c.293C>T, and the sequence has been submitted to NCBI (No. MG597611). CONCLUSION: A novel combination of FUT1 alleles with c.35 C>T and c.293C>T has been identified in an individual with para-Bombay phenotype.


Assuntos
Sistema ABO de Grupos Sanguíneos , Fucosiltransferases/genética , Alelos , Feminino , Genótipo , Humanos , Fenótipo
17.
Am J Cancer Res ; 9(4): 699-713, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105997

RESUMO

Aberrant expression and activation of signal transducer and activator of transcription 3 (STAT3) is implicated in several malignancies, including glioblastoma, and is correlated with poor outcomes in patients with glioblastoma, rendering STAT3 a potential therapeutic target. However, few STAT3 inhibitors have been approved for clinical use. We recently developed an orally active small-molecule compound with anti-STAT3 activity, HJC0152. This study aimed to test the effect of this novel drug on glioblastoma cell lines, and provide possibility to improve clinic prognosis of patients with glioblastoma in the future. In the present study, we aimed to determine the effects of HJC0152 on the growth, proliferation, and chemosensitivity of glioblastoma cell lines and xenograft tumors. We found that HJC0152 inactivated STAT3 via inhibiting phosphorylation of the Tyr705 residue. In vitro, HJC0152 suppressed the proliferation and motility of glioblastoma cells, induced apoptosis, and enhanced the chemosensitivity of glioblastoma cells. Furthermore, HJC0152 inhibited the growth of glioblastoma xenograft tumors in vivo. This study provides a rationale for developing HJC0152 as a STAT3-targeting therapy for treating human glioblastoma in the future.

18.
EBioMedicine ; 40: 198-209, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30738830

RESUMO

BACKGROUND: The resistance to EGF receptor (EGFR) tyrosine kinase inhibitors (TKI) is a major challenge in the treatment of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms behind resistance is therefore an important issue. Here we assessed the role of EGFR pathway substrate 8 (EPS8) and Forkhead box O 3a (FoxO3a) as potentially valuable targets in the resistance of NSCLC . METHODS: The expression levels of EPS8 and FoxO3a in patients with NSCLC (n = 75) were examined by immunohistochemistry staining, while in cells were detected by qPCR and western blot. The effects of EPS8 and FoxO3a on resistance, migration and invasion, cell cycle arrest were detected by MTT, transwell and flow cytometry, respectively. Chromatin immunoprecipitation and luciferase reporter assays were performed to determine the mechanisms of EPS8 expression and FoxO3a regulation. FINDINGS: We observed that the expression of EPS8 inversely correlated with FoxO3a in NSCLC cell lines and NSCLC patients. FoxO3a levels were significantly decreased in tumor tissues compared with para-carcinoma tissues, while EPS8 is opposite. Besides, they play reverse roles in the resistance to gefitinib, the migration and invasion abilities, the cell cycle arrest in vitro and the tumor growth in vivo. Mechanistically, FoxO3a inhibits EPS8 levels by directly binding its gene promoter and they form a negative loop in EGFR pathway. INTERPRETATION: Targeting FoxO3a and EPS8 in EGFR signaling pathway prevents the progression of NSCLC, which implied that the negative loop they formed could served as a therapeutic target for overcoming resistance in NSCLC. FUNDS: National Natural Science Foundation of China, Science and Technology Project of Henan, Outstanding Young Talent Research Fund of Zhengzhou University and the National Scholarship Fund.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteína Forkhead Box O3/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/metabolismo , Feminino , Gefitinibe/farmacologia , Genes Reporter , Xenoenxertos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Camundongos , Modelos Biológicos , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(6): 891-893, 2018 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-30512172

RESUMO

OBJECTIVE: To explore the molecular basis for an individual with Ax28 phenotype of the ABO subtype. METHODS: The ABO group antigens on red blood cells of the proband were identified by monoclonal antibodies. The ABO antibody in serum was detected by standard A, B, O cells. Exons 1 to 7 of the ABO gene were respectively amplified by PCR and directly sequenced. Amplicons for exons 5 to 7 were also sequenced after cloning. RESULTS: Weakened A antigen was detected on red blood cells from the proband. Both anti-A and anti-B antibodies were detected in the serum. Heterozygous 261G/del was detected in exon 6, while heterozygous 467C/T and 830T/C were detected in exon 7 by direct DNA sequencing. After cloning and sequencing, two alleles (O01 and Ax28) were obtained. Compared with A102, the sequence of Ax28 contained one nucleotide changes (T to C) at position 830, which resulted in amino acid change (Val to Ala) at position 277. CONCLUSION: The novel mutation c.830T>C of the galactosaminyltransferase gene may give rise to the Ax28 phenotype.


Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Galactosiltransferases/genética , Alelos , Substituição de Aminoácidos , Éxons , Genótipo , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Deleção de Sequência
20.
Int J Oncol ; 52(4): 1149-1164, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29532870

RESUMO

Abnormal activation of signal transducer and activator of transcription 3 (STAT3) serves a pivotal role in oral squamous cell carcinoma (OSCC) tumor cell invasion into normal tissues or distant organs. However the downstream regulatory network of STAT3 signaling remains unclear. The present study aimed to investigate the potential mechanism underlying how STAT3 triggers enhancer of zeste homolog 2 (EZH2) expression and inhibits microRNA (miR)-200a/b/429 expression in SCC25 and SCC15 cells in vitro and in vivo. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect expression, and numerous functional tests were conducted to explore cancer metastasis. The results indicated that when STAT3 signaling activity was attenuated by Stattic or enhanced with a STAT3 plasmid, the EZH2/miR-200 axis was markedly altered, thus resulting in modulation of the invasion and migration of OSCC cell lines. In addition, loss of function of EZH2 compromised the oncogenic role of STAT3 in both cell lines. F-actin morphology and the expression of epithelial-mesenchymal transition markers were also altered following disruption of the STAT3/EZH2/miR-200 axis. An orthotopic tumor model derived from SCC15 cells was used to confirm that targeting STAT3 or EZH2 suppressed OSCC invasion in vivo. In conclusion, the EZH2/miR-200 axis was revealed to mediate antitumor effects by targeting STAT3 signaling; these findings may provide a novel therapeutic strategy for the treatment of OSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , MicroRNAs/biossíntese , Neoplasias Bucais/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Transição Epitelial-Mesenquimal , Neoplasias de Cabeça e Pescoço/patologia , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/antagonistas & inibidores , Neoplasias Bucais/patologia , Invasividade Neoplásica , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/biossíntese , Carcinoma de Células Escamosas de Cabeça e Pescoço
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