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1.
Mol Cancer ; 20(1): 66, 2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33836754

RESUMEN

BACKGROUND: A novel type of noncoding RNA, circRNA has been reported to participate in the occurrence and development of diseases through many mechanisms. The MAPK pathway is a common signal transduction pathway involved in cell proliferation, inflammation and apoptosis and plays a particularly important role in cancers. However, the role of circRNAs related to the MAPK pathway in gastric cancer has not been explored. METHODS: A bioinformatics analysis was performed to profile and identify the circRNAs involved in the MAPK pathway in gastric cancer. The tumor-suppressive role of circMAPK1 was confirmed both in vitro and in vivo. Mass spectrometry, Western blot and immunofluorescence staining assays were used to validate the existence and expression of MAPK1-109aa. The molecular mechanism of circMAPK1 was investigated by mass spectrometry and immunoprecipitation analyses. RESULTS: In this study, we identified that circMAPK1 (hsa_circ_0004872) was downregulated in gastric cancer tissues compared with adjacent normal tissues. Importantly, lower circMAPK1 expression predicted poor survival in GC patients. CircMAPK1 inhibited the proliferation and invasion of gastric cancer cells in vitro and in vivo. Next, we found that circMAPK1 encoded a novel protein with 109 amino acids in length. Through a series of functional experiments, we confirmed that circMAPK1 exerted a tumor-suppressing effect via the encoded protein MAPK1-109aa. Mechanistically, the tumor suppressor MAPK1-109aa inhibited the phosphorylation of MAPK1 by competitively binding to MEK1, thereby suppressing the activation of MAPK1 and its downstream factors in MAPK pathway. CONCLUSIONS: Our study revealed that circMAPK1 inhibits the malignant biological behavior of gastric cancer cells through its encoded protein MAPK1-109aa. More importantly, circMAPK1 is a favorable predictor for gastric cancer patients and may provide a new therapeutic target in the treatment of gastric cancer.


Asunto(s)
Biomarcadores de Tumor , Sistema de Señalización de MAP Quinasas , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , ARN Circular/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Adulto , Anciano , Secuencia de Aminoácidos , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Susceptibilidad a Enfermedades , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proteína Quinasa 1 Activada por Mitógenos/química , Metástasis de la Neoplasia , Estadificación de Neoplasias , Fosforilación , Neoplasias Gástricas/patología , Carga Tumoral
2.
Opt Express ; 28(11): 16073-16088, 2020 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-32549438

RESUMEN

Coherent optical communication provides optical links with a high spectral efficiency and sensitivity. An essential feature of a coherent optical receiver is to phase lock the optical local oscillator to the carrier of the incoming signal. In this work, we propose and demonstrate, for the first time, a novel coherent optical receiver, where the relative instantaneous phase between the incoming optical carrier and a semiconductor laser (SCL), serving as the optical local oscillator, is first detected using a balanced photodiode, filtered, and used in a feed-forward scheme to modify the phase of the optical local oscillator, effectively recovering the input carrier, which is then used for data recovery. The proposed architecture leverages high-performance on-chip photonic devices to realize a low-power coherent optical receiver without utilizing a phase-locked loop and eliminates the required high data-rate ADC, lowering the complexity of the backend DSP. The photonic part of the implemented prototype was integrated on a 180 nm silicon-on-insulator photonic process within a footprint of 1.0 mm × 0.8 mm. Clock and data recovery at 10 GBaud/s with bit-error-rates better than 10-6 and 10-3 for optical BPSK and QPSK have been demonstrated, respectively.

3.
Pestic Biochem Physiol ; 163: 102-107, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31973845

RESUMEN

Anthracnose is a leaf spot, blossom blight, or fruit rot disease caused by Colletotrichum gloeosporioides (Penz.). It is the most prevalent disease in mango-growing countries worldwide. Lipopeptides, such as those in the iturin family, account for the majority of antifungal secondary metabolites in Bacillus subtilis, Bacillus amyloliquefaciens and Bacillus velezensis, and includes bacillomycin D. Thus far, the mechanism of bacillomycin D's activity has not been clear. In this study, bacillomycin D was isolated from B. velezensis HN-2, which strongly inhibits C. gloeosporioides (Penz.). The median inhibitory concentration of bacillomycin D was 2.162 µg/mL, causing deformation and damage to C. gloeosporioides (Penz.). Bacillomycin D showed more potent activity against C. gloeosporioides (Penz.) than two common fungicides prochloraz and mancozeb. Scanning and transmission electron microscopy revealed that bacillomycin D could injure the cell wall and cell membrane of the hyphae and spores of C. gloeosporioides (Penz.), and the cytoplasm and organelles inside the cell were exuded and formed empty holes. This research clarifies the mechanism underlying bacillomycin D antifungal activity and reveals its high potential as a biopesticide to control phytopathogens.


Asunto(s)
Bacillus , Colletotrichum , Antifúngicos , Péptidos Catiónicos Antimicrobianos , Enfermedades de las Plantas
4.
Opt Express ; 27(8): 10729-10737, 2019 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-31052926

RESUMEN

Direct frequency locking of lasers to RF oscillators has many applications such as high resolution optical frequency synthesis, coherent optical communication, spectroscopy, sensing, and imaging. Here we present a hybrid-integrated opto-electronic loop that directly frequency locks a semiconductor laser to an RF synthesized source using an opto-electronic oscillator with a dispersive optical delay line. Cascaded ring filters, operating near the resonance frequency, provide an enhanced chromatic dispersion with a compact footprint. The electronic chip is integrated in the GlobalFoundries 180 nm CMOS SOI technology and the photonic chip is integrated in the IME 180 nm SOI technology. A tracking range of 0.5 GHz is achieved while consuming 33 mW power. The proposed scheme is used to frequency lock a commercially available DFB laser, reducing the laser frequency fluctuations by an order of magnitude compared to the free-running case.

5.
Opt Express ; 22(13): 16431-8, 2014 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-24977892

RESUMEN

We propose for the first time the Mod-MUX-Ring architecture for microring based WDM transmitter. A prototype Mod-MUX-Ring transmitter with 4 channels and 400 GHz channel spacing is demonstrated and fully characterized at 40 Gb/s channel rate. Under 2.7 V driving voltage, error-free (BER < 10(-12)) operation is achieved on all channels, with 3 dB extinction ratio. Performance comparisons to Lithium Niobate modulators are made.

6.
Opt Express ; 22(23): 28284-91, 2014 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-25402070

RESUMEN

A microring-based silicon modulator operating at 40 Gb/s near 1310 nm is demonstrated for the first time to our knowledge. NRZ-OOK signals at 40 Gb/s with 6.2 dB extinction ratio are observed by applying a 4.8 Vpp driving voltage and biasing the modulator at 7 dB insertion loss point. The energy efficiency is 115 fJ/bit. The transmission performance of 40 Gb/s NRZ-OOK through 40 km of standard single mode fiber without dispersion compensation is also investigated. We show that the link suffers negligible dispersion penalty. This makes the modulator a potential candidate for metro network applications.


Asunto(s)
Diseño Asistido por Computadora , Tecnología de Fibra Óptica/instrumentación , Dispositivos Ópticos , Semiconductores , Procesamiento de Señales Asistido por Computador/instrumentación , Silicio , Telecomunicaciones/instrumentación , Diseño de Equipo
7.
Front Plant Sci ; 15: 1403202, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39049860

RESUMEN

Background: Pepper veinal mottle virus (PVMV) belongs to the genus Potyvirus within the family Potyviridae and is a major threat to pepper production, causing reduction in yield and fruit quality; however, efficient pesticides and chemical treatments for plant protection against viral infections are lacking. Hence, there is a critical need to discover highly active and environment-friendly antiviral agents derived from natural sources. Bacillus spp. are widely utilized as biocontrol agents to manage fungal, bacterial, and viral plant diseases. Particularly, Bacillus velezensis HN-2 exhibits a strong antibiotic activity against plant pathogens and can also induce plant resistance. Methods: The experimental subjects employed in this study were Bacillus velezensis HN-2, benzothiadiazole, and dufulin, aiming to evaluate their impact on antioxidant activity, levels of reactive oxygen species, activity of defense enzymes, and expression of defense-related genes in Nicotiana benthamiana. Furthermore, the colonization ability of Bacillus velezensis HN-2 in Capsicum chinense was investigated. Results: The results of bioassays revealed the robust colonization capability of Bacillus velezensis HN-2, particularly in intercellular spaces, leading to delayed infection and enhanced protection against PVMV through multiple plant defense mechanisms, thereby promoting plant growth. Furthermore, Bacillus velezensis HN-2 increased the activities of antioxidant enzymes, thereby mitigating the PVMV-induced ROS production in Nicotiana benthamiana. Moreover, the application of Bacillus velezensis HN-2 at 5 dpi significantly increased the expression of JA-responsive genes, whereas the expression of salicylic acid-responsive genes remained unchanged, implying the activation of the JA signaling pathway as a crucial mechanism underlying Bacillus velezensis HN-2-induced anti-PVMV activity. Immunoblot analysis revealed that HN-2 treatment delayed PVMV infection at 15 dpi, further highlighting its role in inducing plant resistance and promoting growth and development. Conclusions: These findings underscore the potential of Bacillus velezensis HN-2 for field application in managing viral plant diseases effectively.

8.
Mater Horiz ; 11(16): 3747-3763, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-38895771

RESUMEN

Porous crystalline conjugated macrocyclic materials (CMMs) possess high porosity, tunable structure/function and efficient charge transport ability owing to their planar macrocyclic conjugated π-electron system, which make them promising candidates for applications in energy storage. In this review, we thoroughly summarize the timely development of porous crystalline CMMs in energy storage related fields. Specifically, we summarize and discuss their structures and properties. In addition, their energy storage applications, such as lithium ion batteries, lithium sulfur batteries, sodium ion batteries, potassium ion batteries, Li-CO2 batteries, Li-O2 batteries, Zn-air batteries, supercapacitors and triboelectric nanogenerators, are also discussed. Finally, we present the existing challenges and future prospects. We hope this review will inspire the development of advanced energy storage materials based on porous crystalline CMMs.

9.
Front Genet ; 15: 1377434, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756450

RESUMEN

Background: Gastric cancer (GC) continues to be one of the leading causes of cancer-related deaths globally. Diet significantly influences the incidence and progression of GC. However, the relationship between dietary intake and GC is inconsistent. Methods: A study was conducted with adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2016 to investigate possible associations between 32 dietary factors and GC. To further detect potential causal relationships between these dietary factors and the risk of GC, a two-sample Mendelian randomization (MR) analysis was conducted. The primary method employed was the inverse variance weighted (IVW) analysis, and its results were further validated by four other methods. Results: Of the 35,098 participants surveyed, 20 had a history of GC. Based on the results of weighted logistic multivariate analysis, it was observed that there was a positive correlation between total fat intake [odds ratio (OR) = 1.09, 95% confidence interval (CI): (1.01-1.17), p = 0.03] and GC as well as negative association of dietary monounsaturated fatty acids (MUFAs) intake [OR = 0.83, 95% CI: (0.76-0.92), p < 0.001]. Further evaluations of the odds of GC across the quartiles of dietary MUFAs showed that the top quartile of total MUFA intake was associated with a lower likelihood of GC in three different models [model1: OR = 0.03, 95% CI: (0.00-0.25), p < 0.01; model2: OR = 0.04, 95% CI: (0.00-0.38), p = 0.01; model3: OR = 0.04, 95% CI: (0.00-0.40), p = 0.01]. For the MR analyses, genetic instruments were selected from the IEU Open GWAS project; IVW analysis showed that GC risk was not associated with MUFAs [OR = 0.82, 95% CI: (0.59-1.14), p = 0.23] or the ratio of MUFAs to total fatty acids [OR = 1.00, 95% CI: (0.75-1.35), p = 0.98]. Similar results were observed when using the other MR methods. Conclusion: The NHANES study revealed that consuming MUFAs was linked to a lower risk of GC, although the results of MR analyses do not provide evidence of a causal relationship. Additional research is therefore necessary to clarify these findings.

10.
Opt Express ; 21(3): 3818-25, 2013 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-23481838

RESUMEN

We present measurements of the nonlinear distortions of a traveling-wave silicon Mach-Zehnder modulator based on the carrier depletion effect. Spurious free dynamic range for second harmonic distortion of 82 dB·Hz(1/2) is seen, and 97 dB·Hz(2/3) is measured for intermodulation distortion. This measurement represents an improvement of 20 dB over the previous best result in silicon. We also show that the linearity of a silicon traveling wave Mach-Zehnder modulator can be improved by differentially driving it. These results suggest silicon may be a suitable platform for analog optical applications.


Asunto(s)
Interferometría/instrumentación , Refractometría/instrumentación , Silicio/química , Resonancia por Plasmón de Superficie/instrumentación , Telecomunicaciones/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Modelos Lineales
11.
Opt Express ; 21(23): 28387-93, 2013 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-24514348

RESUMEN

Germanium-on-silicon photodetectors have been heavily investigated in recent years as a key component of CMOS-compatible integrated photonics platforms. It has previously been shown that detector bandwidths could theoretically be greatly increased with the incorporation of a carefully chosen inductor and capacitor in the photodetector circuit. Here, we show the experimental results of such a circuit that doubles the detector 3dB bandwidth to 60 GHz. These results suggest that gain peaking is a generally applicable tool for increasing detector bandwidth in practical photonics systems without requiring the difficult process of lowering detector capacitance.

12.
Cancer Commun (Lond) ; 43(1): 123-149, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36353796

RESUMEN

BACKGROUND: Previous studies have revealed the critical role of transglutaminase 2 (TGM2) as a potential therapeutic target in cancers, but the oncogenic roles and underlying mechanisms of TGM2 in gastric cancer (GC) are not fully understood. In this study, we examined the role and potential mechanism of TGM2 in GC. METHODS: Western blotting, immunohistochemistry, CCK8, colony formation and transwell assays were used to measure TGM2 expression in the GC cells and tissues and to examine the in vitro role of TGM2 in GC. Xenograft and in vivo metastasis experiments were performed to examine the in vivo role of TGM2 in GC. Gene set enrichment analysis, quantitative PCR and western blotting were conducted to screen for potential TGM2 targets involved in GC. Gain/loss-of-function and rescue experiments were conducted to detect the biological roles of STAT1 in GC cells in the context of TGM2. Co-immunoprecipitation, mass spectrometry, quantitative PCR and western blotting were conducted to identify STAT1-interacting proteins and elucidate their regulatory mechanisms. Mutations in TGM2 and two molecules (ZM39923 and A23187) were used to identify the enzymatic activity of TGM2 involved in the malignant progression of GC and elucidate the underlying mechanism. RESULTS: In this study, we demonstrated elevated TGM2 expression in the GC tissues, which closely related to pathological grade, and predicted poor survival in patients with GC. TGM2 overexpression or knockdown promoted (and inhibited) cell proliferation, migration, and invasion, which were reversed by STAT1 knockdown or overexpression. Further studies showed that TGM2 promoted GC progression by inhibiting STAT1 ubiquitination/degradation. Then, tripartite motif-containing protein 21 (TRIM21) was identified as a ubiquitin E3 ligase of STAT1 in GC. TGM2 maintained STAT1 stability by facilitating the dissociation of TRIM21 and STAT1 with GTP-binding enzymatic activity. A23187 abolished the role of TGM2 in STAT1 and reversed the pro-tumor role of TGM2 in vitro and in vivo. CONCLUSIONS: This study revealed a critical role and regulatory mechanism of TGM2 on STAT1 in GC and highlighted the potential of TGM2 as a therapeutic target, which elucidates the development of medicine or strategies by regulating the GTP-binding activity of TGM2 in GC.


Asunto(s)
Proteína Glutamina Gamma Glutamiltransferasa 2 , Factor de Transcripción STAT1 , Neoplasias Gástricas , Humanos , Calcimicina , Línea Celular Tumoral , Guanosina Trifosfato/metabolismo , Proteína Glutamina Gamma Glutamiltransferasa 2/metabolismo , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Neoplasias Gástricas/patología , Ubiquitinación
13.
Front Oncol ; 13: 1169454, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37182139

RESUMEN

Background: For gastric cancer (GC) patients with pylorus outlet obstruction (POO), whether laparoscopic surgery has advantages over open surgery remains unclear. This study aims to investigate the differences between patients with and without POO in open and laparoscopic groups and to determine the differences between laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) in GC patients with POO. Methods: A total of 241 GC patients with POO who underwent distal gastrectomy at the Department of Gastric Surgery of the First Affiliated Hospital of Nanjing Medical University between 2016 and 2021 were included in this study. A total of 1,121 non-POO patients who underwent laparoscopic surgery and 948 non-POO patients who underwent open surgery from 2016 to 2021 were also enrolled in the study. We compared complication rates and hospital stays between open and laparoscopic groups. Results: There was no significant difference for LDG between GC patients with and without POO regarding the overall complication rates (P = 0.063), the Grade III-V complication rate (P = 0.673), and the anastomotic complication rate (P = 0.497) from 2016 to 2021. The patients with POO had longer preoperative hospital stay (P = 0.001) and postoperative hospital stay (P=0.007) compared to patients without POO. No significant difference was observed for open patients between POO and non-POO patients regarding the overall complication rate (P = 0.357), grade III-V complication rate (P = 1.000), and anastomosis-related complication rate (P = 0.766). Compared with open surgery in GC patients with POO (n = 111), the total complication rate of the LDG group was 16.2%, which was significantly lower than that of the open group (26.1%, P = 0.041). No significant differences in the Grade III-V complication rate (P = 0.574) and anastomotic complication rate (P = 0.587) were observed between laparoscopic and open groups. Patients receiving laparoscopic surgery had shorter postoperative hospital stay than open surgery (P = 0.001). More resected lymph nodes (LNs) were also observed in the laparoscopic group (P = 0.0145). Conclusion: The comorbidity of GC with POO does not increase the complication rate after laparoscopic or open distal gastrectomy. In GC patients with POO, laparoscopic surgery shows advantages over open surgery with a lower overall complication rate, shorter postoperative hospital stay, and more harvested lymph nodes. Laparoscopic surgery is a safe, feasible, and effective treatment for GC with POO.

14.
Front Chem ; 11: 1114970, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36825226

RESUMEN

Drug discovery is a costly and time-consuming process with a very high failure rate. Recently, click chemistry and computer-aided drug design (CADD) represent popular areas for new drug development. Herein, we summarized the recent updates in click and computational chemistry for drug discovery and development including clicking to effectively synthesize druggable candidates, synthesis and modification of natural products, targeted delivery systems, and computer-aided drug discovery for target identification, seeking out and optimizing lead compounds, ADMET prediction as well as compounds synthesis, hopefully, inspires new ideas for novel drug development in the future.

15.
J Exp Clin Cancer Res ; 41(1): 296, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36217165

RESUMEN

BACKGROUND: Liver metastasis (LM) is a major obstacle to the prognosis of gastric cancer (GC) patients, but the molecular mechanism underlying gastric cancer liver metastasis (GC-LM) remains unknown. Exosomes have been identified as an important mediator of communication between tumor cells and the microenvironment. Therefore, we sought to investigate the effects of primary GC cells on the liver microenvironment and the role of exosomal microRNAs (exo-miRNA) in GC-LM. METHODS: Sequential differential centrifugation, transmission electron microscopy and NanoSight analysis were used to extract and characterize exosomes. MicroRNA sequencing in GC-derived exosomes and mRNA sequencing in PMA-treated THP-1 cells were used to identify differentially expressed miRNAs in exosomes and the functional targets of exosomal miR-519a-3p (exo-miR-519a-3p) in macrophages, respectively. Tracing and internalization of exosomes and transfer of exo-miR-519a-3p were observed by immunofluorescence. Tubule formation assays, aortic ring assays, and exosome-educated GC-LM model were used to investigate the roles of GC-derived exosomes and exo-miR-519a-3p in angiogenesis and GC-LM. Luciferase reporter assay, qRT-PCR, Western blot, ELISA, flow cytometry and immunofluorescence were used to investigate the regulatory mechanism of exo-miR-519a-3p at GC-LM. RESULTS: The expression level of miR-519a-3p in serum exosomes was significantly higher in GC-LM patients than in patients without LM, and high expression of exo-miR-519a-3p indicates a worse prognosis. GC-derived exosomes are mainly accumulated in the liver and internalized by intrahepatic macrophages. Mechanistically, exo-miR-519a-3p activates the MAPK/ERK pathway by targeting DUSP2, thereby causing M2-like polarization of macrophages. M2-like polarized macrophages accelerate GC-LM by inducing angiogenesis and promoting intrahepatic premetastatic niche formation. CONCLUSIONS: Our results indicate that exo-miR-519a-3p plays a critical role in mediating crosstalk between primary GC cells and intrahepatic macrophages and is a potential therapeutic target for GC-LM.


Asunto(s)
Exosomas , Neoplasias Hepáticas , MicroARNs , Neoplasias Gástricas , Línea Celular Tumoral , Proliferación Celular , Exosomas/genética , Exosomas/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Macrófagos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neovascularización Patológica/metabolismo , ARN Mensajero/metabolismo , Neoplasias Gástricas/patología , Microambiente Tumoral/genética
16.
Clin Transl Med ; 12(1): e708, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35075806

RESUMEN

BACKGROUND: Chemotherapy can significantly improve the disease-free survival and overall survival of patients with advanced gastric cancer (GC). 5-fluorouracil (5-FU) is frequently applied in the clinic, acting as a first-line chemotherapy drug of advanced GC, which could be used alone or combining platinum drugs. However, its efficacy is significantly attenuated by chemoresistance, which is associated with patients' poor survival. Recently, there is evidence suggesting that dysregulation of autophagy may contribute to drug resistance in cancer, and circular RNAs (circRNAs) also take part in chemoresistance. However, whether circRNAs participate in 5-FU chemoresistance through autophagy remains largely unknown. METHODS: RNA sequencing technologies and bioinformatics analysis were performed in GC. Sanger sequencing, Actinomycin D assay and RNase R assay confirmed the circular structure of circular CPM (circCPM). Various cell line models and animal models were used to explore related functions in vitro and in vivo. Quantitative Real-time PCR (qRT-PCR), fluorescence in situ hybridization, ribonucleic acid; (RNA) pulldown assays, RNA binding protein immunoprecipitation assays and Luciferase reporter assays were applied to explore involved pathways. RESULTS: circCPM was up-regulated in 5-FU resistant GC cell lines and tissue. Moreover, high circCPM expression is positively associated with poor survival. Silencing circCPM greatly improved chemosensitivity in vitro and in vivo. Mechanistically, it directly binds to miR-21-3p in the cytoplasm and therefore increases the expression of PRKAA2, contributing to the activation of autophagy and chemoresistance. CONCLUSION: Our results reveal that circCPM has a crucial role in regulating GC autophagy and 5-FU resistance by targeting PRKAA2. It may function as a new theory basis for assessing the curative effect of GC and reversing 5-FU chemoresistance.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Neoplasias Gástricas/genética , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/farmacología , Autofagia/genética , Proteínas Ligadas a GPI/agonistas , Proteínas Ligadas a GPI/metabolismo , Humanos , Estimación de Kaplan-Meier , Metaloendopeptidasas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , MicroARNs/uso terapéutico
17.
Clin Transl Med ; 12(1): e707, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35061934

RESUMEN

Gastric cancer (GC) ranks third in mortality among all cancers worldwide. Circular RNAs (circRNAs) play an important role in the occurrence and development of gastric cancer. Forkhead box P2 (FOXP2), as a transcription factor, is closely associated with the development of many types of tumours. However, the regulatory network between FOXP2 and circRNAs remains to be explored. In our study, circST3GAL6 was significantly downregulated in GC and was associated with poor prognosis in GC patients. Overexpression of circST3GAL6 inhibited the malignant behaviours of GC cells, which was mediated by inducing apoptosis and autophagy. In addition, we demonstrated that circST3GAL6 regulated FOXP2 through the mir-300 sponge. We further found that FOXP2 inhibited MET Proto-Oncogene (MET), which was the initiating factor that regulated the classic AKT/mTOR pathway of autophagy. In conclusion, our results suggested that circST3GAL6 played a tumour suppressive role in gastric cancer through miR-300/FOXP2 axis and regulated apoptosis and autophagy through FOXP2-mediated transcriptional inhibition of the MET axis, which may become a potential target for GC therapy.


Asunto(s)
Autofagia/efectos de los fármacos , Sialiltransferasas/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Animales , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Modelos Animales de Enfermedad , Factores de Transcripción Forkhead/efectos de los fármacos , Ratones , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Proteínas Proto-Oncogénicas c-met/efectos de los fármacos , Sialiltransferasas/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Neoplasias Gástricas/prevención & control , Serina-Treonina Quinasas TOR/efectos de los fármacos , beta-Galactosida alfa-2,3-Sialiltransferasa
18.
Cell Death Dis ; 13(3): 266, 2022 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-35338119

RESUMEN

Circular RNAs (circRNAs) play vital regulatory roles in the progression of multiple cancers. In our study, transcriptome analysis and self-organizing maps (SOM) were applied to screen backbone circRNAs in gastric cancer (GC). Upon validation of the expression patterns of screened circRNAs, gain- and loss-of-function assays were performed in vitro and in vivo. Underlying mechanisms were investigated using RNA pull-down, luciferase reporter assay and RNA immunoprecipitation. The expression of circTHBS1 was significantly increased in GC and associated with poor prognosis. CircTHBS1 facilitated the malignant behavior and epithelial-to-mesenchymal transition of GC cells. Mechanistically, circTHBS1 sponged miR-204-5p to promote the expression of Inhibin Subunit Beta A (INHBA). Moreover, circTHBS1 could enhance the HuR-mediated mRNA stability of INHBA, which subsequently activated the TGF-ß pathway. Our research identified circTHBS1 as an oncogenic circRNA that enhances GC malignancy by elevating INHBA expression, providing new insight and a feasible target for the diagnosis and treatment of GC.


Asunto(s)
MicroARNs , Neoplasias Gástricas , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Subunidades beta de Inhibinas , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Mensajero/genética , Neoplasias Gástricas/patología , Trombospondina 1
19.
Nanomaterials (Basel) ; 12(16)2022 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-36014610

RESUMEN

The formation of polymeric micro-patterns on various substrates via a photolithography procedure has been widely used in semiconductor fabrication. Standard polymer patterns are usually fabricated via photosensitive polymer varnishes, in which large amounts of potentially harmful solvents with weight ratios over 50 wt% have to be removed. In the current work, a novel pattern-formation methodology via solvent-free electrospun photosensitive polymeric fibrous membranes (NFMs) instead of the conventional photosensitive solutions as the starting photoresists was proposed and practiced. For this purpose, a series of preimidized negative auto-photosensitive polyimide (PSPI) resins were first prepared via the two-step chemical imidization procedure from the copolymerization reactions of 3,3',4,4'-benzophenonetetracarboxylic- dianhydride (BTDA) and two ortho-methyl-substituted aromatic diamines, including 3,3',5,5'-tetramethyl-4,4'-diaminodiphenylmethane (TMMDA) and 3,7-diamino-2,8-dimethyl- dibenzothiophene sulfone (TSN). The derived homopolymer PI-1 (BTDA-TMMDA) and the copolymers, including SPI-2~SPI-6, with the molar ratio of 5~25% for TSN in the diamine units, showed good solubility in polar solvents. Then, a series of PSPI NFMs were fabricated via standard electrospinning procedure with the developed PSPI solutions in N,N-dimethylacetamide (DMAc) with a solid content of 25 wt% as the starting materials. The derived PSPI NFMs showed good thermal stability with 5% weight loss temperatures higher than 500 °C in nitrogen. Meanwhile, the derived PSPIs showed good photosensitivity to the ultraviolet (UV) emitting wavelengths of i-line (365 nm), g-line (405 nm) and h-line (436 nm) of the high-pressure mercury lamps in both forms of transparent films and opaque NFMs. Fine micro-patterns with a line width of around 100 µm were directly obtained from the representative SPI-4 NFM via standard photolithography procedure.

20.
Cell Death Dis ; 12(11): 968, 2021 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-34671022

RESUMEN

Gastric cancer (GC) ranks the third among global cancer-related mortality, especially in East Asia. Angiogenesis plays an important role in promoting tumor progression, and clinical trials have demonstrated that anti-angiogenesis therapy is effective in GC management. Natriuretic peptide receptor A (NPRA) functions significantly in promoting GC development and progression. Whether NPRA can promote angiogenesis of GC remains unclear. Tumor samples collection and immunohistochemical experiment showed that the expression of NPRA was positively correlated with the expression of CD31 and vessel density. In vivo and in vitro analysis showed that NPRA could promote GC-associated angiogenesis and tumor metastasis. Results of Co-IP/MS showed that NPRA could prevent HIF-1α from being degraded by binding to HIF-1α. Protection of HIF-1α improved VEGF levels and thus promoted angiogenesis. In summary, NPRA protected HIF-1α from proteolysis by binding to HIF-1α, increased the expression of HIF-1α, and promoted GC angiogenesis. This study has discovered a new mechanism for NPRA to promote gastric cancer development and a new regulatory mechanism for HIF-1α.


Asunto(s)
Neovascularización Patológica/metabolismo , Receptores del Factor Natriurético Atrial/metabolismo , Neoplasias Gástricas/irrigación sanguínea , Neoplasias Gástricas/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Modelos Animales de Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones Desnudos , Modelos Biológicos , Estadificación de Neoplasias , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Pronóstico , Proteolisis , Transducción de Señal , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Regulación hacia Arriba/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
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