Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Carcinogenesis ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39234990

RESUMO

Adenocarcinoma of the esophagogastric junction (AEG) has received widespread attention because of its increasing incidence. However, the molecular mechanism underlying tumor progression remains unclear. Here, we report that the downregulation of Ubiquitin-specific peptidase 49 (USP49) promotes ferroptosis in OE33 and OE19 cells, thereby inhibiting cell proliferation in vitro and in vivo, whereas the overexpression of USP49 had the opposite effect. In addition, USP49 downregulation promoted AEG cell radiotherapy sensitivity. Moreover, overexpression of Glutathione PeroXidase 4 (GPX4) reversed the ferroptosis and proliferation inhibition induced by USP49 knockdown. Mechanistically, USP49 deubiquitinates and stabilizes Shc SH2-domain binding protein 1 (SHCBP1), subsequently facilitating the entry of ß-catenin into the nucleus to enhance GPX4 transcriptional expression. Finally, high USP49 expression was correlated with shorter overall survival in patients with AEG. In summary, our findings identify USP49 as a novel regulator of ferroptosis in AEG cells, indicating that USP49 may be a potential therapeutic target in AEG.

2.
Cell Commun Signal ; 22(1): 168, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454413

RESUMO

BACKGROUND: The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. METHODS: Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). RESULTS: In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. CONCLUSIONS: Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.


Assuntos
Neoplasias Colorretais , Animais , Humanos , Camundongos , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos , Neoplasias Colorretais/patologia , Linfócitos do Interstício Tumoral , Proteínas Nucleares , Proteínas Repressoras , Evasão Tumoral
3.
BMC Neurol ; 22(1): 13, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996385

RESUMO

BACKGROUND: Parkinson's disease (PD) is associated with enteric nervous system dysfunction and gut microbiota dysbiosis. Short-chain fatty acids (SCFAs), derived from gut microbiota, are supposed to anticipate PD pathogenesis via the pathway of spinal cord and vagal nerve or the circulatory system. However, the serum concentration of SCFAs in PD patients is poorly known. This study aims to investigate the exact level of SCFAs in PD patients and its correlation with Parkinson's symptoms. METHODS: 50 PD patients and 50 healthy controls were recruited, and their demographic and clinical characteristics were collected. The serum concentration of SCFAs was detected using a gas chromatography-mass spectrometer. SCFAs were compared between PD and control groups. The correlation between serum SCFAs and Parkinson's symptoms and the potential effects of medications on the serum SCFAs was analyzed. RESULTS: Serum propionic acid, butyric acid and caproic acid were lower, while heptanoic acid was higher in PD patients than in control subjects. However, only the serum level of propionic acid was correlated with Unified Parkinson's Disease Rating Scale (UPDRs) part III score (R = -0.365, P = 0.009), Mini-mental State Examination (MMSE) score (R = -0.416, P = 0.003), and Hamilton Depression Scale (HAMD) score (R = 0.306, P = 0.03). There was no correlation between other serum SCFAs and motor complications. The use of trihexyphenidyl or tizanidine increased the serum concentration of propionic acid. CONCLUSIONS: Serum SCFAs are altered in PD patients, and the decrease of serum propionic acid level is correlated with motor symptoms, cognitive ability and non-depressed state. Thus, the gut microbial-derived SCFAs potentially affect Parkinson's symptoms through the blood circulation. Propionic acid supplementation might ameliorate motor and non-motor symptoms of PD patients, although clinical trials are needed to test this hypothesis.


Assuntos
Microbioma Gastrointestinal , Doença de Parkinson , Cognição , Ácidos Graxos Voláteis , Humanos , Doença de Parkinson/tratamento farmacológico
4.
Endocr Pract ; 28(8): 760-766, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35550181

RESUMO

OBJECTIVE: To evaluate the genotype-phenotype relationship and the effect of treatment on the clinical course of osteogenesis imperfecta (OI). METHODS: We established a Chinese hospitalized cohort with OI and followed them up for an average of 6 years. All patients were confirmed as having OI using whole-exome sequencing. We analyzed the genotype-phenotype relationship based on different types, pathogenic mechanisms, and gene inheritance patterns of OI. Additionally, we assessed whether there was a difference in treatment efficacy based on genotype. RESULTS: One hundred sixteen mutations in 6 pathogenic genes (COL1A1, COL1A2, IFITM5, SERPINF1, FKBP10, and WNT1) were identified in 116 patients with type I, III, IV, V, VI, XI, or XV OI. Compared with patients with COL1A1 mutations, patients with COL1A2 mutations were younger at the time of the first fracture, whereas other phenotypes were similar. When 3 groups (helical, haploinsufficiency, and non-collagen I gene mutations) were compared, patients with helical mutations were the shortest and most prone to dentinogenesis imperfecta. Patients with haploinsufficiency mutations were the oldest at the time of the first fracture. Moreover, patients with non-collagen I gene mutations were least susceptible to blue sclerae and had the highest fracture frequency. Furthermore, there were some minor phenotypic differences among non-collagen I gene mutations. Interestingly, pamidronate achieved excellent results in the treatment of patients with OI, and the treatment effect appeared to be unrelated to their genotypes. CONCLUSION: Our findings indicated a genotype-phenotype relationship and a similar effect of pamidronate treatment in patients with OI, which could provide a basis for guiding clinical treatment and predicting OI prognosis.


Assuntos
Osteogênese Imperfeita , China , Colágeno Tipo I/genética , Seguimentos , Genótipo , Humanos , Mutação , Osteogênese Imperfeita/tratamento farmacológico , Osteogênese Imperfeita/genética , Pamidronato/uso terapêutico , Fenótipo
5.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4042-4047, 2022 Aug.
Artigo em Zh | MEDLINE | ID: mdl-36046893

RESUMO

Attapulgite(ATP), as a fertilizer slow-release agent and soil conditioner, has shown remarkable effect in improving the utilization rate of fertilizer and the yield and quality of agricultural products and Chinese medicinal materials. This study aims to explore the effect of ATP on the growth and root quality of Angelica sinensis. To be specific, Mingui 1 was used, and through the pot(soil culture) experiment in the Dao-di producing area, the effects of conventional chemical fertilizer added with ATP on the morphology, photosynthesis, soil respiration, and content of ferulic acid and volatile oil in roots of Mingui 1 were detected. The underlying mechanism was discussed from the perspective of source-sink relationship. The results showed that ATP, via the fertilizer slow-release effect, could meet the needs of A. sinensis for nutrients at the root expansion stage, improve the net photosynthetic rate of leaves and aboveground biomass of plants, and promote the transfer and accumulation of nutrients from the aboveground part(source) to the underground root(sink) in advance during the dry matter accumulation period of roots, so as to improve the root weight per plant. ATP can increase the content of total ferulic acid(the sum of free ferulic acid and coniferyl ferulate), the main effective component of Angelicae Sinensis Radix, by promoting the synthesis of ferulic acid in the roots and the transformation to coniferyl ferulate. However, it had little effect on the content of volatile oil. ATP had certain influence on soil respiration, which needs to be further explored from root activity, rhizosphere microorganisms, and soil microorganisms. This study can lay a basis for soil remediation and improvement and ecological cultivation of A. sinensis.


Assuntos
Angelica sinensis , Óleos Voláteis , Trifosfato de Adenosina , Angelica sinensis/química , Ácidos Cumáricos , Fertilizantes/análise , Compostos de Magnésio , Óleos Voláteis/química , Raízes de Plantas/química , Compostos de Silício , Solo
6.
Zhongguo Zhong Yao Za Zhi ; 46(22): 5736-5743, 2021 Nov.
Artigo em Zh | MEDLINE | ID: mdl-34951161

RESUMO

The medicinal plants with roots and rhizomes as the medicinal parts account for about 1/3 of Chinese medicinal herbs. Root and rhizome medicinal materials are widely used in clinical practice, whereas their wild resource reserves are insufficient to meet the market demand. With the expansion of planting areas, the formation of large-scale production areas, and the increase in planting years, diseases and insect pests of these medicinal plants, which are diverse and have broad transmission routes, strong concealment, and heavy damage, have become more and more serious. The prevention and control of these diseases and insect pests is characterized by multiple ways of pesticide application, large consumption of pesticides, susceptibility to soil barrier, difficulty in the control, and unstable control efficiency. Organophosphorus pesticides(OPPs) are widely used in the cultivation of Chinese medicinal plants because of their diverse varieties, broad-spectrum, good efficacy, and low residues, and have a positive effect on the yield and quality of Chinese medicinal materials. However, the abuse of OPPs not only increases the planting cost, but also affects the quality and safety of Chinese medicinal plants, the safety of clinical use of Chinese medicine, and the ecological safety of production areas. This paper reviewed the research and development progress of OPPs, the registration status of OPPs used in root and rhizome medicinal materials, residue limit standards, residue status, and rapid detection technology progress of OPPs. This review aims to provide research ideas and references for standardizing the use of OPPs in root and rhizome medicinal materials, reducing OPP residues, and establishing a fast, efficient, accurate, and reliable method for the detection of OPP residues in Chinese herbal medicine.


Assuntos
Resíduos de Praguicidas , Praguicidas , Plantas Medicinais , Compostos Organofosforados , Resíduos de Praguicidas/análise , Praguicidas/análise , Rizoma/química
7.
J Cell Mol Med ; 24(19): 11133-11145, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32827244

RESUMO

Acylglycerol kinase (AGK) uses adenosine triphosphate (ATP) and acylglycerol to generate adenosine diphosphate (ADP) and acyl-sn-glycerol 3-phosphate in cells. Recent evidence has demonstrated that dysregulated AGK expression is associated with the development of various human cancers. This study investigated the effects of AGK on gastric cancer cell proliferation and carcinogenesis and explored the underlying molecular events. AGK expression was up-regulated in gastric cancer and was associated with poor prognosis in gastric cancer patients. AGK overexpression increased gastric cancer proliferation, invasion capacity and the expression of the epithelial-mesenchymal transition markers in vitro. Conversely, the knockdown of AGK expression reduced gastric cancer cell proliferation in vitro and in nude mouse tumour cell xenografts. Importantly, AGK expression was associated with the YAP1 expression in gastric cancer cells and tissues. YAP1 expression also transcriptionally induced AGK expression through the binding of TEAD to the AGK gene promoter. However, AGK expression inhibited the activation of the Hippo pathway proteins and induced YAP1 nuclear localization to enhance the transcription activity of YAP1/TEADs. In conclusion, the study demonstrates that AGK is not only a novel target of the Hippo-YAP1 pathway, but that it also positively regulates YAP1 expression, thus forming a YAP1-AGK-positive feedback loop.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/genética , Fatores de Transcrição/metabolismo , Regulação para Cima/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Enzimológica da Expressão Gênica , Células HEK293 , Humanos , Camundongos Nus , Invasividade Neoplásica , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Neoplasias Gástricas/patologia , Transcrição Gênica , Proteínas de Sinalização YAP
8.
Langmuir ; 36(20): 5483-5491, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32357012

RESUMO

The interfacial adhesion between silicon oxide surfaces is normally believed to be governed by the surface chemistry of the topmost surface affecting the water contact angle and hydrogen bonding interactions. In the case of a silicon wafer, the physical structure of the native oxide at the surface can vary drastically depending on the aging process; thus, not only the surface chemistry but also the history of surface treatment can also have a profound impact on nanoasperity adhesion. This study reports the effect of aging conditions (ambient air, liquid water, and liquid ethanol) on the nanoasperity adhesion behaviors of a silicon surface. When the silicon surface is kept in liquid alcohol, the surface remains hydrophobic, and adhesion in ambient air can be explained with the capillary effect of the liquid meniscus condensed around the annulus of the nanoasperity contact. When the silicon surface is oxidized in ambient air, the surface gradually becomes hydrophilic, and the strongly hydrogen-bonded water network of adsorbed water plays a dominant role in the nanoasperity interfacial adhesion force. When the silicon surface is aged in liquid water, the interfacial adhesion force measured in ambient air is significantly larger than the value predicted from the theoretical model based on the water contact angle and the hydrogen bonding interaction at the topmost surface. This is because the surface layer oxidized in liquid water is gel-like and thus can swell upon uptake of water from the humid air. To fully encompass all these behaviors, a solid-adsorbate-solid model predicting the adhesion force is developed by introducing a fitting parameter ß, which can be adjusted depending on the adsorbed water structure and the swelling capacity of the oxidized surface layer.

9.
World J Surg Oncol ; 18(1): 324, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33292276

RESUMO

BACKGROUND: Follistatin-like 1 (FSTL1) plays a central role in the progression of tumor and tumor immunity. However, the effect of FSTL1 on the prognosis and immune infiltration of gastric cancer (GC) remains to be elucidated. METHODS: The expression of FSTL1 data was analyzed in Oncomine and TIMER databases. Analyses of clinical parameters and survival data were conducted by Kaplan-Meier plotter and immunohistochemistry. Western blot assay and real-time quantitative PCR (RT-qPCR) were used to analyze protein and mRNA expression, respectively. The correlations between FSTL1 and cancer immune infiltrates were analyzed by Tumor Immune Estimation Resource (TIME), Gene Expression Profiling Interactive Analysis (GEPIA), and LinkedOmics database. RESULTS: The expression of FSTL1 was significantly higher in GC tissues than in normal tissues, and bioinformatic analysis and immunohistochemistry (IHC) indicated that high FSTL1 expression significantly correlated with poor prognosis in GC. Moreover, FSTL1 was predicted as an independent prognostic factor in GC patients. Bioinformatics analysis results suggested that FSTL1 mainly involved in tumor progression and tumor immunity. And significant correlations were found between FSTL1 expression and immune cell infiltration in GC. CONCLUSIONS: The study effectively revealed useful information about FSTL1 expression, prognostic values, potential functional networks, and impact of tumor immune infiltration in GC. In summary, FSTL1 can be used as a biomarker for prognosis and evaluating immune cell infiltration in GC.


Assuntos
Proteínas Relacionadas à Folistatina , Neoplasias Gástricas , Biomarcadores , Proteínas Relacionadas à Folistatina/genética , Humanos , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia
10.
Zhongguo Zhong Yao Za Zhi ; 45(9): 2031-2035, 2020 May.
Artigo em Zh | MEDLINE | ID: mdl-32495549

RESUMO

The long-term and extensive use of chemical fertilizers and pesticides in the cultivation of Chinese materia medica has resulted in serious soil ecological and environmental problems such as secondary salinization, soil consolidation, soil acidification, continuous cropping obstacles, micro-ecological imbalance, and serious soil pests and diseases in the production areas of Chinese materia medica. Therefore, promoting the ecological planting of Chinese materia medica is the only way for the production of Chinese materia medica. Attapulgite(ATP) is a kind of water-rich magnesium-rich aluminosilicate clay mineral with layered and chain structure. It has abundant reserves in China, possesses nano-material properties, strong adsorption and ion exchange properties, and has huge high value utilization space. ATP and its functional products have the potential of water and fertilizer conservation, regulating soil structure and micro-ecology, and are widely used in ecological planting of Chinese materia medica. This paper reviews the resource distribution, structural characteristics, the research and application progress in soil ecological effects of ATP, and prospects the application prospects of it in the ecological planting of Chinese materia medica.


Assuntos
Medicamentos de Ervas Chinesas , Materia Medica , China , Compostos de Magnésio , Medicina Tradicional Chinesa , Compostos de Silício , Solo
11.
J Cell Mol Med ; 23(12): 8076-8089, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31559693

RESUMO

Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a transcriptional repressor involved in regulating gene expression and other biological processes, including tumorigenesis. However, the clinical significance and roles of IRF2BP2 in human gastric cancer (GC) remain uncertain. Clinical GC tissues were obtained from GC patients at the First Affiliated Hospital of Nanchang University. Immunohistochemistry (IHC) was conducted to detect the IRF2BP2 protein in clinical paraffin specimens. Cell proliferation, migration and invasion were evaluated by MTT, colony formation assays and transwell assays. Co-immunoprecipitation was conducted to detect the interaction between TEA domain family members 4 (TEAD4) and vestigial-like family member 4 (VGLL4) or Yes-associated protein 1 (YAP1). Dual-luciferase reporter assay was used to confirm the binding of miR-101-3p to the 3'-UTR. The expression of IRF2BP2 was significantly higher in GC tissues than in normal tissues. Patients with higher IRF2BP2 protein expression had lower survival. IRF2BP2 knockdown inhibited proliferation, migration, invasion and epithelial-mesenchymal transition in GC cells. IRF2BP2 knockdown decreased the mRNA and protein levels of connective tissue growth factor (CTGF). The interaction between IRF2BP2 and VGLL4 increased the binding of TEAD4 to YAP1, resulting in the transcriptional coactivation of CTGF. In addition, miR-101-3p suppressed the expression of CTGF by directly targeting the 3'-UTR of IRF2BP2. Taken together, these findings provide a model for the role of miR-101-3p-IRF2BP2-CTGF signalling axis in GC and a novel insight into the mechanism of GC progression and metastasis.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Gástricas/metabolismo , Fatores de Transcrição/metabolismo , Regiões 3' não Traduzidas , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Fator de Crescimento do Tecido Conjuntivo/genética , Proteínas de Ligação a DNA/genética , Bases de Dados Genéticas , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Transcrição de Domínio TEA , Fatores de Transcrição/genética , Transplante Heterólogo , Proteínas de Sinalização YAP
12.
J Sports Sci ; 37(24): 2826-2834, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31500501

RESUMO

To comprehensively shed light on whether viewing football games is associated with a higher risk of cardiovascular disease (CVD). Electronic databases were searched through 17 May 2018. All studies focusing on the association between viewing football matches and the fatal or non-fatal CVD were identified. Viewing football matches was associated with a higher risk of fatal overall CVD (RR: 1.06, 95%CI: 1.01-1.12) in both men (RR: 1.13, 95%CI: 1.004-1.28) and women (RR: 1.08, 95%CI: 1.01-1.15). Subgroup analysis showed that failure of the team has a higher risk of fatal overall CVD (RR: 1.29, 95%CI: 1.15-1.45). However, lower risk of fatal overall CVD from spectators was observed when team obtained a victory (RR: 0.80, 95%CI: 0.66-0.96). For non-fatal CVD, viewing football matches was associated with a higher risk of non-fatal overall CVD (RR: 1.24, 95%CI: 1.09-1.41) in both men (RR: 1.73, 95%CI: 1.12-2.69) and women (RR: 1.25, 95%CI: 1.08-1.45). Subgroup analysis showed that viewing football matches was associated with a higher risk of non-fatal myocardial infarction (RR: 1.20, 95%CI: 1.04-1.38) in both men and women (RR: 1.51, 95%CI: 0.99-2.28; RR: 1.21, 95%CI: 1.08-1.36, respectively). No significant increase was found in fatal or non-fatal stroke. Viewing football matches was associated with a higher risk of the fatal and non-fatal CVD, especially in male spectators. The victory of team could have a lower risk of fatal CVD. Therefore, precautionary measures should be required for the reduction of healthcare burden in football matches.


Assuntos
Doenças Cardiovasculares/mortalidade , Futebol , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Atividades de Lazer , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade
13.
Biochem Biophys Res Commun ; 505(3): 843-849, 2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30297104

RESUMO

Long non-coding RNAs (lncRNAs) function as vital regulators of the progression of various diseases, particularly cancers. In the present study, utilizing the Cancer Genome Atlas (TCGA) data set and a series of cell experiments and clinical tissue samples assays, we found that LINC00662 expression was significantly up-regulated in gastric cancer (GC) tissues and cell lines. High expression of LINC00662 predicted poor prognosis compared to in patients showing low expression. Knockdown of LINC00662 expression decreased GC cell proliferation and increased the chemo-sensitivity of GC cells. Further, we demonstrated that knockdown of LINC00662 suppressed the Hippo-YAP1 signaling pathway in GC cells. Mechanistically, LINC00662 regulated YAP1-mediated GC cell proliferation by sponging miR-497-5p. Overall, our results revealed a critical role for the LINC00662-miR-497-5p-YAP1 axis in GC cell growth, providing a new target for GC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , RNA Longo não Codificante/análise , Neoplasias Gástricas/patologia , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Linhagem Celular Tumoral , Proliferação de Células , Via de Sinalização Hippo , Humanos , MicroRNAs/metabolismo , MicroRNAs/fisiologia , Fosfoproteínas/fisiologia , Prognóstico , Proteínas Serina-Treonina Quinases/fisiologia , RNA Longo não Codificante/farmacologia , Fatores de Transcrição , Proteínas de Sinalização YAP
14.
Biochem Biophys Res Commun ; 503(4): 2370-2375, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30017188

RESUMO

YAP1, a vital effector of Hippo pathway, promotes cancer development via transcriptionally regulating a batch of target genes involved in various signaling pathways, including proliferation, apoptosis, and cell drug sensitivity. Recently, circular RNAs (circRNAs) have been shown to control gene expression post-transcriptionally and become a new layer of gene regulation. However, whether circRNAs play roles in YAP1-induced tumorigenesis is still largely elusive. Here, we identify circRNA-000425 as a new inhibitory target of YAP1, and also find that it binds to miR-17/miR-106b, and thus suppresses cancer cell growth induced by these miRNAs. circRNA-000425 is revealed as a YAP1 target through circRNA microarray analysis of RNAs extracted from cells treated with or without YAP1 siRNAs, and further confirmed by RT-q-PCR and ChIP assays. Interestingly, bioinformatics analysis, luciferase assay, and RT-q-PCR results showed that circRNA-000425 binds to miR-17 and miR-106b, but not let-7a, and rescues the inhibitory effect of miR-17/miR-106 on the expressions of both p21 and BIM. In addition, colony formation and MTT assay showed that circRNA-000425 inhibits cancer cell growth induced by miR-17. These findings reveal a mechanism by which YAP1 promotes oncogenic activities of miR-17 and miR-106b through transcriptionally inhibiting circRNA-000425 expression.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Fosfoproteínas/genética , RNA/genética , Proliferação de Células , Humanos , Interferência de RNA , RNA Circular , RNA Interferente Pequeno/genética , Fatores de Transcrição , Proteínas de Sinalização YAP
15.
Molecules ; 22(10)2017 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-29048389

RESUMO

Inhibitors of Rho kinase (ROCK) have potential therapeutic applicability in a wide range of diseases, such as hypertension, stroke, asthma and glaucoma. In a previous article, we described the lead discovery of DL0805, a new ROCK I inhibitor, showing potent inhibitory activity (IC50 6.7 µM). Herein, we present the lead optimization of compound DL0805, resulting in the discovery of 24- and 39-fold more-active analogues 4a (IC50 0.27 µM) and 4b (IC50 0.17 µM), among other active analogues. Moreover, ex-vivo studies demonstrated that 4a and 4b exhibited comparable vasorelaxant activity to the approved drug fasudil in rat aortic rings. The research of a preliminary structure-activity relationship (SAR) indicated that the target compounds containing a ß-proline moiety have improved activity against ROCK I relative to analogues bearing an α-proline moiety, and among the series of the derivatives with a ß-proline-derived indazole scaffold, the inhibitory activity of the target compounds with a benzyl substituent is superior to those with a benzoyl substituent.


Assuntos
Indazóis/síntese química , Inibidores de Proteínas Quinases/síntese química , Vasodilatadores/síntese química , Quinases Associadas a rho/antagonistas & inibidores , Animais , Desenho de Fármacos , Humanos , Indazóis/química , Indazóis/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Relação Estrutura-Atividade , Vasodilatadores/química , Vasodilatadores/farmacologia
16.
Org Biomol Chem ; 14(32): 7715-21, 2016 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-27461927

RESUMO

A novel formal synthesis of Beraprost (1) is described. The tricyclic cyclopent[b]benzofuran core is efficiently prepared from (-)-Corey lactone diol in 12 steps with an overall yield of 37.4%. Key features of the strategy include a ring-closing metathesis reaction and aromatization to form the tricyclic cyclopenta[b]benzofuran framework, and selective halogenation/formylation to install the butyrate side-chain.


Assuntos
Benzofuranos/síntese química , Ciclopentanos/síntese química , Epoprostenol/análogos & derivados , Benzofuranos/química , Ciclopentanos/química , Epoprostenol/síntese química , Epoprostenol/química , Estrutura Molecular
17.
Org Biomol Chem ; 14(5): 1805-13, 2016 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-26757679

RESUMO

The relative and absolute configurations of xiamenmycin A, a benzopyran compound isolated from Streptomyces xiamenensis 318 with a highly potent anti-fibrotic activity, have been characterized through the total synthesis. The key steps include the construction of the 3-chromanol moiety via Sharpless epoxidation followed by regio- and diastereo-selective cyclization and introduction of the threonine moiety at a later stage via Pd-catalysed aminocarbonylation in a one-pot procedure. The stereochemical assignment of natural xiamenmycin A has been accordingly revised to be 2R, 3S, 3'S, 4'R.


Assuntos
Benzopiranos/química , Benzopiranos/síntese química , Treonina/análogos & derivados , Estrutura Molecular , Estereoisomerismo , Treonina/síntese química , Treonina/química
18.
J Asian Nat Prod Res ; 18(10): 976-87, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27256638

RESUMO

Xiamenmycin C, a potent anti-fibrotic natural product, and all of its stereoisomers have been synthesized and their structures were fully characterized. Based on this study, the originally proposed structure of xiamenmycin C has been accordingly revised to be 2R,3S.


Assuntos
Benzopiranos/síntese química , Produtos Biológicos/síntese química , Treonina/análogos & derivados , Benzopiranos/química , Produtos Biológicos/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Estereoisomerismo , Treonina/síntese química , Treonina/química
19.
J Asian Nat Prod Res ; 16(6): 629-39, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24911263

RESUMO

Racemic 4-demethylenglerin A (1'), a simplified analog of the guaiane-type sesquiterpene englerin A (1), has been synthesized. The cyclic hydrocarbon core structure was built through modified Metz approach using epoxynitrile cyclization and direct Aldol reaction to prepare the precursor of RCM. The primary cytotoxicity test summarized that C4 methyl has marked impacts on the bioactivity.


Assuntos
Sesquiterpenos de Guaiano/síntese química , Ciclização , Humanos , Estrutura Molecular , Phyllanthus/química , Sesquiterpenos de Guaiano/química , Estereoisomerismo , Relação Estrutura-Atividade
20.
Front Pediatr ; 12: 1347556, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596247

RESUMO

Purpose: This study aims to demonstrate the use of the cartilaginous to osseous acetabular angle ratio (AAR) in surgical decision-making for hip dysplasia. Methods: Data were collected from patients who underwent an MRI of the hip after conservative treatment for developmental dysplasia of the hip between August 2019 and 2022. The data included demographic information as well as an anteroposterior pelvic radiograph. The osseous acetabular index (OAI) was measured using x-ray, while the cartilaginous acetabular index (CAI) and the cartilaginous acetabulum head index (CAHI) were measured using MRI. The square of the CAI to OAI, AAR, was calculated. The patients in the residual hip dysplasia (RHD) group were categorized as having an OAI above 20°. During the postoperative follow-up, we evaluated the patients in this group who underwent Bernese triple pelvic osteotomy. Data on surgical patients with an observation period that exceeded 1 year were collected and analyzed. The distribution of the AAR among the different groups was analyzed. A receiver operating characteristic (ROC) predictive model was constructed using the AAR of the patients in the normal and surgical groups to evaluate the need for surgery. Results: It was found that there was a significant difference in the OAI, CAI, CAHI, and AAR between the RHD group (OAI 26.15 ± 3.90°, CAI 11.71 ± 4.70°, CAHI 79.75 ± 6.27%, and AAR 5.88 ± 4.24) and the control group patients (OAI 16.77 ± 5.39°, CAI 6.16 ± 3.13°, CAHI 85.05 ± 4.91%, and AAR 2.71 ± 2.08) (p < 0.001). A total of 93.5% of the control group patients had an AAR ≤5, while only 6.5% had an AAR >5. The results of postoperative imaging follow-up were "excellent" in 52 patients and "good" in 3, while the functional follow-up results were excellent in 53 and good in 2. In 15 patients, the observation period exceeded 1 year. The mean observation period was 633.1 ± 259.6 days and the preoperative CAHI was 71.7 ± 4.8%. Of the patients with an AAR >5, a substantial 94.8% (55/58) of them were reported to have undergone surgery, while all patients with an AAR less than or equal to 5 did not undergo surgery (91/91). Based on the ROC, a cutoff value of 5.09 was identified for the need for surgery in children with RHD. Conclusions: A surgical decision for residual hip dysplasia can be based on the AAR. An AAR >5 may be a potential indicator for surgical intervention in patients with RHD.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA