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1.
Chem Biodivers ; 21(4): e202301711, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38372187

RESUMEN

Stored products are constantly infested by insects, so finding eco-friendly bioinsecticides for insect management is important. The work aimed to assess the insecticidal and repellent activity of essential oil (EO) from Hedychium glabrum S. Q. Tong, Hedychium coronarium Koen., and Hedychium yunnanense Gagnep. against Tribolium castaneum, Lasioderma serricorne, and Liposcelis bostrychophila. Results showed that 88 chemical components were identified in the extracted Hedychium EOs, indicating that they exhibited diversity in components. According to principal component analysis (PCA), the composition of the EO from the H. yunnanense stem and leaf (EOHYSL) was significantly different from other EOs due to the different organs and species. The biological activity also varied continuously with plant species and organs. Only the EO of H. yunnanense (EOHY) showed strong fumigant toxicity. While in the contact tests, EOHGR showed the strongest toxicity effect on L. bostrychophila, with a LC50 value of 71.76 µg/cm2, which was closest to the positive control (Pyrethrin). All EOs had remarkable repellent activities against the three target insects, and repellency increased with concentration. According to the results of the comprehensive score, EOHY had the highest potential, which ranged from 0.7999 to 0.8689. Thus, Hedychium EOs possess potential biorational traits to be biological insecticides.


Asunto(s)
Escarabajos , Repelentes de Insectos , Insecticidas , Aceites Volátiles , Tribolium , Zingiberaceae , Animales , Aceites Volátiles/toxicidad , Aceites Volátiles/química , Insectos , Insecticidas/química , Repelentes de Insectos/farmacología , Repelentes de Insectos/química
2.
Biochem Cell Biol ; 101(4): 284-293, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-36821837

RESUMEN

Studies in the past decade have shown that lipid droplets stored in liver cells under starvation are encapsulated by autophagosomes and fused to lysosomes via the endocytic system. Autophagy responds to a variety of environmental factors inside and outside the cell, so it has a complex signal regulation network. To this end, we first explored the role of Hedgehog (Hh) in autophagy and lipid metabolism. Treatment of normal mouse liver cells with SAG and GDC-0449 revealed elevated phosphorylation of AMP-activated protein kinase (AMPK) and increased lipidation of LC3. SAG, and GDC-0449 were agonist and antagonist of Smoothened (Smo) in canonical Hh pathway, respectively, but they played a consistent role in the regulation of autophagy in hepatocytes. Moreover, SAG and GDC-0449 did not affect the expression of glioma-associated oncogene (Gli1) and patched 1, suggesting the absence of canonical Hh signaling in hepatocytes. We further knocked down the Smo and found that the effects of SAG and GDC-0449 disappeared, indicating that the non-canonical Smo pathway was involved in the regulation of autophagy in hepatocytes. In addition, SAG and GDC-0449 promoted lipid degradation and inhibited lipid production signals. Knockdown of Smo slowed down the rate of lipid degradation rather than Sufu or Gli1, indicating that Hh signaling regulated the lipid metabolism via Smo. In summary, activates AMPK via Smo to promote autophagy and lipid degradation.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Proteínas Hedgehog , Ratones , Animales , Proteínas Hedgehog/metabolismo , Proteína con Dedos de Zinc GLI1/genética , Hepatocitos/metabolismo , Autofagia , Lípidos , Receptores Acoplados a Proteínas G/metabolismo
3.
Ann Hematol ; 101(12): 2617-2625, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36178488

RESUMEN

The clinical characteristics and prognosis of intracranial hemorrhage (ICH) in patients with hematological diseases remain controversial. This study aimed to describe the clinical characteristics and explore the prognostic factors in such patients. A total of 238 ICH patients with a hematological disease were recruited from the Institute of Hematology and Blood Diseases Hospital, China, from January 2015 to April 2020. The Cox proportional hazards model was used to identify the prognostic factors for 30-day mortality in ICH patients with a hematological disease. There were 123 cases of acute leukemia (AL), 20 of myelodysplasia/myeloproliferative neoplasm, 35 of aplastic anemia (AA), 29 of immune thrombocytopenia (ITP), 19 of congenital/acquired coagulation factor deficiency, and 12 of other hematological diseases. Furthermore, 121 patients presented with a multi-site hemorrhage (MSH), 58 with a single-site hemorrhage in the brain parenchyma (PCH), 23 with a subarachnoid hemorrhage, 33 with a subdural hemorrhage (SH), and three with an epidural hemorrhage. The Cox proportional hazards model indicated association of SH (vs PCH, hazard ratio [HR]: 0.230; 95% confidence interval [CI]: 0.053-0.996; P = 0.049), low white blood cells (≤ 100 × 109/L vs > 100 × 109/L, HR: 0.56; 95% CI: 0.348-0.910; P = 0.019), AA (vs AL, HR: 0.408; 95% CI: 0.203-0.821; P = 0.012), and ITP (vs AL, HR: 0.197; 95% CI: 0.061-0.640; P = 0.007) with improved 30-day mortality. However, increased age (HR: 1.012; 95% CI: 1.001-1.022; P = 0.034), MSH (vs PCH, HR: 1.891; 95% CI: 1.147-3.117; P = 0.012), and a disturbance of consciousness (HR: 1.989; 95% CI: 1.269-3.117; P = 0.003) were associated with increased risk of 30-day mortality. In conclusion, in this study, we revealed the clinical characteristics of Chinese ICH patients with a hematological disease. Moreover, we identified risk factors (age, white blood cells, AA, ITP, SH, MSH, and a disturbance of consciousness) that may influence 30-day mortality.


Asunto(s)
Anemia Aplásica , Enfermedades Hematológicas , Leucemia Mieloide Aguda , Trombocitopenia , Humanos , Anemia Aplásica/complicaciones , Hemorragia Cerebral/complicaciones , Enfermedades Hematológicas/complicaciones , Hematoma Subdural , Hemorragias Intracraneales/etiología , Leucemia Mieloide Aguda/complicaciones , Pronóstico , Factores de Riesgo , Trombocitopenia/complicaciones
4.
Chem Biodivers ; 18(11): e2100374, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34453492

RESUMEN

Thymus quinquecostatus Celak. of the Lamiaceae family has a long history of dual use of medicine and food with high economic value, and has been proved to have good antioxidative, antimicrobial, and antidiabetic activities. Essential oil (EO) extracted from the aerial part of T. quinquecostatus was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC/MS) and GC. Totally 45 compounds were identified accounting for 98.5 % of the EO. The major constituents of the EO were linalool (52.003 %), borneol (10.911 %) and anethole (5.325 %). Fumigant, contact and repellent activity of T. quinquecostatus essential oil (EO) against Tribolium castaneum (Coleoptera: Tenebrionidae), Lasioderma Serricorne (Coleoptera: Anobiidae), Liposcelis bostrychophila (Psocoptera: Liposcelididae) were evaluated in this work. T. quinquecostatus EO and three major constituents showed varying degrees of insecticidal and repellent activities to three stored-product insects. Anethole stated the best fumigant and contact activity than others did to all three insect species. EO and compounds showed general repellent activity against three target insects. This work suggests that the EO of T. quinquecostatus has promising potential to be developed into botanical pesticides and repellents controlling pest damage in warehouses and grain stores.


Asunto(s)
Repelentes de Insectos/farmacología , Insectos/efectos de los fármacos , Insecticidas/farmacología , Aceites Volátiles/farmacología , Componentes Aéreos de las Plantas/química , Thymus (Planta)/química , Animales , Repelentes de Insectos/química , Repelentes de Insectos/aislamiento & purificación , Insecticidas/química , Insecticidas/aislamiento & purificación , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación
5.
J Oleo Sci ; 73(5): 761-772, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38692898

RESUMEN

Volatile secondary metabolites of plants interact with environments heavily. In this work, characteristic components of Michelia yunnanensis essential oils (EOs) were isolated, purified and identified by column chromatography, GC-MS and NMR. Leaves of M. yunnanensis were collected monthly and extracted for EOs to investigate chemical and insecticidal activity variations as well as potential influencing environments. Different organs were employed to reveal distribution strategies of characteristic components. Results of insecticidal activities showed that all EOs samples exerted stronger contact activity to Lasioderma serricorne, but repellent effect was more efficient on Tribolium castaneum. One oxygenated sesquiterpene was isolated from EOs, basically it could be confirmed as (+)-cyclocolorenone (1). It exerted contact toxicity to L. serricorne (LD 50 = 28.8 µg/adult). Chemical analysis showed that M. yunnanensis leaves in reproductive period would produce and accumulate more 1 than in vegetative period. Moreover, reproductive organs (flowers and fruits) contained more 1 than vegetative organs (leaves and twigs). Partial correlation analysis indicated that temperature-related elements positively correlated with the relative content of 1.


Asunto(s)
Insecticidas , Aceites Volátiles , Hojas de la Planta , Tribolium , Animales , Insecticidas/aislamiento & purificación , Insecticidas/análisis , Hojas de la Planta/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Tribolium/efectos de los fármacos , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/análisis , Repelentes de Insectos/análisis , Repelentes de Insectos/aislamiento & purificación , Repelentes de Insectos/farmacología , Temperatura
6.
JCI Insight ; 9(6)2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38358805

RESUMEN

Suppressor of fused (SUFU) is widely regarded as a key negative regulator of the sonic hedgehog (SHH) morphogenic pathway and a known tumor suppressor of medulloblastoma (MB). However, we report here that SUFU expression was markedly increased in 75% of specimens compiled in a tissue array comprising 49 unstratified MBs. The SUFU and GLI1 expression levels in this MB array showed strong positive correlation, which was also identified in a large public data set containing 736 MBs. We further report that increasing Sufu gene dosage in mice caused preaxial polydactyly, which was associated with the expansion of the Gli3 domain in the anterior limb bud and heightened Shh signaling responses during embryonic development. Increasing Sufu gene dosage also led to accelerated cerebellar development and, when combined with ablation of the Shh receptor encoded by Patched1 (Ptch1), promoted MB tumorigenesis. These data reveal multifaceted roles of SUFU in promoting MB tumorigenesis by enhancing SHH signaling. This revelation clarifies potentially counterintuitive clinical observation of high SUFU expression in MBs and may pave way for novel strategies to reduce or reverse MB progression.


Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Polidactilia , Ratones , Animales , Meduloblastoma/genética , Meduloblastoma/patología , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Transformación Celular Neoplásica/genética , Factores de Transcripción , Neoplasias Cerebelosas/genética , Polidactilia/genética
7.
Cell Biosci ; 13(1): 15, 2023 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-36683064

RESUMEN

BACKGROUND: Medulloblastoma (MB) is one of the most common malignant pediatric brain tumors. Metastasis and relapse are the leading causes of death in MB patients. The initiation of the SHH subgroup of MB (SHH-MB) is due to the aberrant activation of Sonic Hedgehog (Shh) signaling. However, the mechanisms for its metastasis are still unknown. RESULTS: AMP-dependent protein kinase (AMPK) restrains the activation of Shh signaling pathway, thereby impeding the proliferation of SHH-MB cells. More importantly, AMPK also hinders the growth and metastasis of SHH-MB cells by regulating NF-κB signaling pathway. Furthermore, Vismodegib and TPCA-1, which block the Shh and NF-κB pathways, respectively, synergistically restrained the growth, migration, and invasion of SHH-MB cells. CONCLUSIONS: This work demonstrates that AMPK functions through two signaling pathways, SHH-GLI1 and NF-κB. AMPK-NF-κB axis is a potential target for molecular therapy of SHH-MB, and the combinational blockade of NF-κB and Shh pathways confers synergy for SHH-MB therapy.

8.
Cell Biosci ; 13(1): 208, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37964396

RESUMEN

BACKGROUND: Except for gene fusions, FGFR2 genetic alterations in intrahepatic cholangiocarcinomas (ICCs) have received limited attention, leaving patients harboring activating FGFR2 gene mutations with inadequate access to targeted therapies. EXPERIMENTAL DESIGN: We sought to survey FGFR2 genetic alterations in ICC and pan-cancers using fluorescence in situ hybridization and next-generation sequencing. We conducted an analysis of the clinical and pathological features of ICCs with different FGFR2 alterations, compared FGFR2 lesion spectrum through public databases and multicenter data, and performed cellular experiments to investigate the oncogenic potential of different FGFR2 mutants. RESULTS: FGFR2 gene fusions were identified in 30 out of 474 ICC samples, while five FGFR2 genetic alterations aside from fusion were present in 290 ICCs. The tumors containing FGFR2 translocations exhibited unique features, which we designated as the "FGFR2 fusion subtypes of ICC". Molecular analysis revealed that FGFR2 fusions were not mutually exclusive with other oncogenic driver genes/mutations, whereas FGFR2 in-frame deletions and site mutations often co-occurred with TP53 mutations. Multicenter and pan-cancer studies demonstrated that FGFR2 in-frame deletions were more prevalent in ICCs (0.62%) than in other cancers, and were not limited to the extracellular domain. We selected representative FGFR2 genetic alterations, including in-frame deletions, point mutations, and frameshift mutations, to analyze their oncogenic activity and responsiveness to targeted drugs. Cellular experiments revealed that different FGFR2 genetic alterations promoted ICC tumor growth, invasion, and metastasis but responded differently to FGFR-selective small molecule kinase inhibitors (SMKIs). CONCLUSIONS: FGFR2 oncogenic alterations have different clinicopathological features and respond differently to SMKIs.

9.
J Biol Chem ; 286(15): 13502-11, 2011 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-21317289

RESUMEN

Suppressor of fused (Sufu) is an essential negative regulator of the sonic hedgehog (Shh) pathway, but little is known about how Sufu itself is normally regulated. Here, we report that Sufu is phosphorylated at Ser-342 and Ser-346 by GSK3ß and cAMP-dependent protein kinase A (PKA), respectively, and phosphorylation at this dual site stabilizes Sufu against Shh signaling-induced degradation. We further show that localization of Sufu in the primary cilium is induced by Shh signaling and is required for the turnover of both phosphorylated and total Sufu. Perturbing Sufu phosphorylation with PKA inhibitors or replacing Ser-346 with alanine reduced the stay and replacing Ser-342 and Ser-346 with aspartic acid prolonged the stay of Sufu in the cilia. Finally, ciliary localization of Gli2/3 also required Smo and was similarly influenced by perturbations of PKA activity or mutations at the dual Sufu phosphorylation site. Thus, Shh likely induced trafficking of phospho-Sufu into the primary cilium in a complex with Gli2/3, and dephosphorylation triggered a retrograde export, allowing Sufu to be degraded by the ubiquitin-proteasome system.


Asunto(s)
Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Proteínas Represoras/metabolismo , Sustitución de Aminoácidos , Animales , Cilios/genética , Cilios/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Glucógeno Sintasa Quinasa 3/genética , Glucógeno Sintasa Quinasa 3 beta , Células HEK293 , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones , Mutación Missense , Células 3T3 NIH , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosforilación/fisiología , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Estabilidad Proteica , Transporte de Proteínas/fisiología , Proteínas Represoras/genética , Ubiquitina/genética , Ubiquitina/metabolismo , Proteína Gli2 con Dedos de Zinc , Proteína Gli3 con Dedos de Zinc
10.
Rev Assoc Med Bras (1992) ; 68(4): 470-475, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35649069

RESUMEN

OBJECTIVE: Heat shock protein A2 has been reported to be tightly associated with tumorigenesis and tumor progression. This study aimed to determine the oncogenic and immunological roles of Heat shock protein A2 in pancreatic cancer by bioinformatics. METHODS: Expression of Heat shock protein A2 in tumorous and normal specimens of pancreatic cancer was analyzed using the Cancer Genome Atlas and the Cancer Genome Atlas + Genotype-Tissue Expression data sets, respectively. Relationships of Heat shock protein A2 expression with immune infiltrates in pancreatic cancer were assessed. Heat shock protein A2-associated coexpressed genes in pancreatic cancer were obtained, followed by the implementation of enrichment analysis. RESULTS: The data demonstrated that Heat shock protein A2 was significantly overexpressed in tumorous samples compared with normal samples. Heat shock protein A2 expression was remarkably positively interrelated with CD8+ T cell, neutrophil, dendritic cell, and macrophage, but not with CD4+ T and B cells. Heat shock protein A2 expression was markedly positively relevant to both cancer-associated fibroblast and endothelial cell. Enrichment data revealed that Heat shock protein A2 was intimately involved in the tumorigenesis and progression of pancreatic cancer. CONCLUSION: Heat shock protein A2 is upregulated in pancreatic cancer and is closely associated with tumor immunity and aggressive progression.


Asunto(s)
Proteínas HSP70 de Choque Térmico , Neoplasias Pancreáticas , Carcinogénesis/genética , Biología Computacional , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/inmunología , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas
11.
J Oleo Sci ; 71(3): 435-443, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35236800

RESUMEN

Stored products have been damaged by insects. Multiple approaches for pest management are employed. Among these approaches, botanical insecticide is an emerging one. This work investigated the pest management potential of Magnolia coriacea and Magnolia macclurei essential oils (EOs) to three major stored-product insects, namely the red flour beetle, cigarette beetle and booklouse. Magnolia coriacea and M. macclurei EOs showed promising contact toxicity to the cigarette beetle, with LD50 values of 11.7 and 12.3 µg/adult. The contact toxicity of M. coriacea EOs to the booklouse (LC50 = 95.5 µg/cm2) was much stronger than that of M. macclurei EOs (LC50 = 245.4 µg/cm2). To explore the contribution of individual compounds to insecticidal activity of EOs, chemical analysis was performed by GC-MS. Results showed that nerolidol (27.84%), agarospirol (18.34%), elixene (15.84%) and helminthogermacrene (12.69%) were major compounds of M. coriacea EOs, ß-guaiene (60.31%) and elixene (20.42%) dominated in M. macclurei EOs. Nerolidol and ß-guaiene showed contact activity to three insect species. Nerolidol showed stronger contact toxicity to the red flour beetle and cigarette beetle than M. coriacea EOs did, both samples were similar to the booklouse. ß-Guaiene was much stronger to the red flour beetle and booklouse, but weaker to the cigarette beetle than M. macclurei EOs did. The repellent effects of EOs and compounds were at various levels. Generally, results suggested that the contact toxic potential of samples could serve as management for the cigarette beetle and booklouse, while repellent effect would be used to control the red flour beetle.


Asunto(s)
Escarabajos , Repelentes de Insectos , Insecticidas , Magnolia , Aceites Volátiles , Sesquiterpenos , Tribolium , Animales , Repelentes de Insectos/química , Repelentes de Insectos/farmacología , Insectos , Insecticidas/química , Aceites Volátiles/química , Sesquiterpenos/toxicidad
12.
J Oleo Sci ; 71(7): 1075-1084, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35691834

RESUMEN

In recent years, secondary metabolites of plants have attracted researchers' interest as a substitute for synthetic insecticides with many advantages. Elsholtzia kachinensis is an annual herb with medicinal and edible value. In this study, the essential oil (EO) of the aerial part of E. kachinensis was extracted by hydrodistillation, and GC-MS analysed essential oil components. The results show that carvone and dehydroelsholtzia ketone are the main components of the essential oil, accounting for 32.298% and 31.540%, respectively. EO, carvone and dehydroelsholtzia ketone are used to determine the effects against stored-product insects Lasioderma serricorne, Tribolium castaneum, Sitophilus oryzae and Liposcelis bostrychophila. The essential oil showed the most vital contact and fumigation toxicity to L. serricorne, of which LD50 and LC50 values were 3.85 µg/adult and 7.74 mg/L air, respectively. S. oryzae did not show repellent activity, but the repellent rate of the other three species reached 90% under EO treatment at a concentration of 78.63 nL/cm2. Therefore, the essential oil of E. kachinensis has an insecticidal effect and has the potential to be developed as a new eco-friendly insecticide.


Asunto(s)
Escarabajos , Repelentes de Insectos , Insecticidas , Aceites Volátiles , Plantas Medicinales , Tribolium , Animales , Medicina de Hierbas , Repelentes de Insectos/análisis , Insecticidas/análisis , Insecticidas/toxicidad , Cetonas/análisis , Aceites Volátiles/análisis , Aceites Volátiles/toxicidad , Verduras
13.
J Food Prot ; 85(4): 686-692, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35051268

RESUMEN

ABSTRACT: Artemisia songarica Schrenk is a dominant sand fixation plant growing in the People's Republic of China. At present, there are rare studies on the chemical composition and biological activity of A. songarica. The chemical composition of the original oil was analyzed by gas chromatography-mass spectrometry, and 16 compounds were determined. The main compounds were bisabolol oxide II (28.7%), nerolidol (18.6%), bisabolol (12.9%), bisaboloxide A (10.0%), and spathulenol (6.0%). The contact toxicity and repellent activity of A. songarica essential oil and four selected compounds (bisabolol, geranyl butyrate, nerolidol, and santalol) were assessed against Tribolium castaneum Herbst and Liposcelis bostrychophila Badonnel. Bioassays showed that the crude essential oil exhibited strong insecticide and repellent activities against both pests. Santalol possessed the strongest contact toxicity (50% lethal dose [LD50] = 1.29 µg per adult) against T. castaneum. Nerolidol, santalol, and geranyl butyrate showed fair contact activity against L. bostrychophila. In particular, geranyl butyrate exhibited outstanding activity (LD50 = 11.53 µg/cm2). In addition, all of the four compounds did not detect a difference between compounds and the positive control (P > 0.05) against two pests at five tested concentrations. These results indicated that A. songarica and its selected compounds could be used as prospective insecticidal and repellent agents for further development and use.


Asunto(s)
Repelentes de Insectos , Insecticidas , Aceites Volátiles , Tribolium , Animales , Humanos , Repelentes de Insectos/análisis , Repelentes de Insectos/química , Repelentes de Insectos/farmacología , Insecticidas/farmacología , Aceites Volátiles/química , Aceites Volátiles/farmacología , Estudios Prospectivos
14.
J Biol Chem ; 285(34): 26599-607, 2010 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-20534588

RESUMEN

Vertebrate muscle differentiation is coordinated by an intricate network of transcription factors requiring proliferating myogenic precursors to withdraw irreversibly from the cell cycle. Recent studies have implicated a large number of microRNAs exerting another layer of control in many aspects of muscle differentiation. By annealing to short recognition sequences in the 3'-untranslated region, microRNAs attenuate target gene expression through translation repression or mRNA degradation. Here, we show that miR-214 promotes myogenic differentiation in mouse C2C12 myoblasts at a step preceding the induction of p21 and myogenin. Blocking miR-214 function with a 2'-O-methylated double-stranded inhibitor maintained C2C12 cells in the active cell cycle, thereby inhibiting the myogenic differentiation. By global gene expression profiling, we identified the proto-oncogene N-ras as one of miR-214 targets. Furthermore, manipulating the N-Ras level with small interfering RNA or adenovirus-mediated forced expression either augmented or attenuated the effect of miR-214, respectively. Thus, our data uncovered a novel microRNA-mediated mechanism that controls myogenic differentiation.


Asunto(s)
Diferenciación Celular , Genes ras , MicroARNs/fisiología , Mitosis , Mioblastos/citología , Animales , Línea Celular , Regulación hacia Abajo/genética , Perfilación de la Expresión Génica , Ratones , Desarrollo de Músculos
15.
Cell Death Dis ; 12(3): 256, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-33692336

RESUMEN

Chromosomal translocations involving fibroblast growth factor receptor 2 (FGFR2) gene at the breakpoints are common genetic lesions in intrahepatic cholangiocarcinoma (ICC) and the resultant fusion protein products have emerged as promising druggable targets. However, predicting the sensitivity of FGFR2 fusions to FGFR kinase inhibitors is crucial to the prognosis of the ICC-targeted therapy. Here, we report identification of nine FGFR2 translocations out of 173 (5.2%) ICC tumors. Although clinicopathologically these FGFR2 translocation bearing ICC tumors are indistinguishable from the rest of the cohort, they are invariably of the mass-forming type originated from the small bile duct. We show that the protein products of FGFR2 fusions can be classified into three subtypes based on the breaking positions of the fusion partners: the classical fusions that retain the tyrosine kinase (TK) and the Immunoglobulin (Ig)-like domains (n = 6); the sub-classical fusions that retain only the TK domain without the Ig-like domain (n = 1); and the non-classical fusions that lack both the TK and Ig-like domains (n = 2). We demonstrate that cholangiocarcinoma cells engineered to express the classical and sub-classical fusions show sensitivity to FGFR-specific kinase inhibitors as evident by the suppression of MAPK/ERK and AKT/PI3K activities following the inhibitor treatment. Furthermore, the kinase-deficient mutant of the sub-classical fusion also lost its sensitivity to the FGFR-specific inhibitors. Taken together, our study suggests that it is essential to determine the breakpoint and type of FGFR2 fusions in the small bile duct subtype of ICC for the targeted treatment.


Asunto(s)
Neoplasias de los Conductos Biliares/genética , Biomarcadores de Tumor/genética , Colangiocarcinoma/genética , Fusión Génica , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Translocación Genética , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antineoplásicos/farmacología , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Resistencia a Antineoplásicos/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Terapia Molecular Dirigida , Células 3T3 NIH , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal
16.
Gland Surg ; 10(7): 2140-2149, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34422585

RESUMEN

BACKGROUND: Heat shock protein A2 (HSPA2) is known to relate to the pathogenesis and progress of cancer. This study aimed to investigate the connection between HSPA2 and early postsurgical relapse of pancreatic cancer (PC). METHODS: Expression of HSPA2 in 85 pairs of cancerous and matched noncancerous samples was determined by immunostaining method. The relationship between HSPA2 expression and early postsurgical recurrence was assessed using logistic regression. The performance and potential application of HSPA2 expression to predict early postsurgical recurrence was evaluated by receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). RESULTS: HSPA2 expression in tumor specimens was markedly elevated compared with non-tumor specimens. Logistic regression analysis indicated that HSPA2 upregulation was an independent risk marker for early postsurgical recurrence of PC. ROC curve analysis and DCA demonstrated that both the area under the curve (AUC) and the net benefit of HSPA2 expression were higher than those of other clinicopathologic features in predicting early postsurgical relapse of PC. The combination of HSPA2 expression with other malignant clinicopathologic characteristics had greater AUC and net benefit relative to them alone in predicting early postsurgical recurrence. CONCLUSIONS: Upregulated HSPA2 independently predicts early postsurgical recurrence of PC and has superior predictive performance and potential application value when combined with malignant clinicopathologic features. Our findings reveal that HSPA2 is a promising predictor for early postoperative relapse of PC.

17.
Biochim Biophys Acta Mol Cell Res ; 1868(12): 119124, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34419491

RESUMEN

Autophagy is a highly conservative self-digestion process to maintain intracellular homeostasis and to ensure the survival of cells under stress. Activation of Sonic Hedgehog (Shh) signaling depends on the normal endocytic degradation of pathway receptor Patched1 (Ptch1). It is unclear whether autophagy participates in the receptor endocytosis and modulates Shh signaling transduction. Here we found that blocking macroautophagy attenuates Shh signaling due to the failed transport of Smoothened (Smo) into primary cilia. At the upstream of Smo, Ptch1 was poly-ubiquitinated through K63-conjugated ubiquitin chains. Macroautophagy participates Shh-induced degradation of poly-ubiquitinated Ptch1, contributing to the activation of Shh signaling.


Asunto(s)
Autofagia , Proteínas Hedgehog/metabolismo , Receptor Patched-1/metabolismo , Proteolisis , Animales , Células Cultivadas , Cilios/metabolismo , Células HEK293 , Humanos , Ratones , Transducción de Señal , Receptor Smoothened/metabolismo , Ubiquitinación
18.
Cell Death Discov ; 7(1): 120, 2021 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-34021128

RESUMEN

Although E3 ligase Speckle type BTB/POZ protein (SPOP) promotes tumorigenesis by acting as a key regulatory hub in clear cell renal cell carcinoma (ccRCC), the detailed molecular mechanism remains unclear. Here, we demonstrate that a well-known tumor suppressor, Suppressor of Fused (SUFU), is downregulated by SPOP. Interestingly, this downregulation depends on cullin-3(Cul3)-SPOP E3 ligase, but SUFU is not a direct substrate of SPOP. Phosphatase and tensin homolog (PTEN), a ubiquitinated substrate of SPOP, is involved in SPOP-mediated SUFU reduction. Importantly, inhibition of SUFU leads to elevated SHH and WNT signaling, consequently rescuing the reduced proliferation, migration, and invasion abilities of ccRCC cells caused by SPOP-knockdown. Moreover, combinatorial treatment with SHH and WNT inhibitors shows more effective for suppressing ccRCC cell proliferation and aggressiveness. These findings demonstrate that a novel SPOP-PTEN-SUFU axis promotes ccRCC carcinogenesis by activating SHH and WNT pathway, providing a new treatment strategy for ccRCC.

19.
Daru ; 29(2): 469-475, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34142352

RESUMEN

BACKGROUND: Several species of Verbenaceae have been widely used in medicine, and some species of Verbenaceae have been observed good insecticidal activity, such as Lantana camara and Vitex negundo. There is no report about repellent activity of Clerodendrum bungei Steud. (C. bungei) against stored product insects. The chemical composition of C. bungei essential oil (EO) were identified, repellent activity of methanol extract, EO of C. bungei and two main components of EO against T. castaneum, L. serricorne and L. bostrychophila were evaluated for the first time. RESULTS: EO of C. bungei was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS) and GC. A total of 25 components of the C. bungei EO were identified. The principal compounds in the EO were myristicin (75.0%), 2,2,7,7-Tetramethyltricyclo[6.2.1.0(1,6)]undec-4-en-3-one (4.1%) and linalool (3.4%). Results of bioassays indicated that C. bungei EO exerted strong repellent activity against three target insects. As main constituents, myristicin and linalool also had certain repellency. CONCLUSION: This work suggests that the EO of C. bungei has promising potential to develop into botanical repellents for the control of pest damage in warehouses and grain stores.


Asunto(s)
Clerodendrum/química , Repelentes de Insectos/química , Aceites Volátiles/análisis , Aceites de Plantas/análisis , Monoterpenos Acíclicos/farmacología , Derivados de Alilbenceno/farmacología , Animales , Dioxolanos/farmacología , Cromatografía de Gases y Espectrometría de Masas , Repelentes de Insectos/farmacología , Neoptera/efectos de los fármacos , Neoptera/fisiología , Aceites Volátiles/aislamiento & purificación , Aceites Volátiles/farmacología , Aceites de Plantas/aislamiento & purificación , Aceites de Plantas/farmacología
20.
Cell Biosci ; 11(1): 47, 2021 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-33653390

RESUMEN

BACKGROUND: Skeletal development and maintenance are complex processes known to be coordinated by multiple genetic and epigenetic signaling pathways. However, the role of long non-coding RNAs (lncRNAs), a class of crucial epigenetic regulatory molecules, has been under explored in skeletal biology. RESULTS: Here we report a young patient with short stature, hypothalamic dysfunction and mild macrocephaly, who carries a maternally inherited 690 kb deletion at Chr.1q24.2 encompassing a noncoding RNA gene, DNM3OS, embedded on the opposite strand in an intron of the DYNAMIN 3 (DNM3) gene. We show that lncRNA DNM3OS sustains the proliferation of chondrocytes independent of two co-cistronic microRNAs miR-199a and miR-214. We further show that nerve growth factor (NGF), a known factor of chondrocyte growth, is a key target of DNM3OS-mediated control of chondrocyte proliferation. CONCLUSIONS: This work demonstrates that DNM3OS is essential for preventing premature differentiation of chondrocytes required for bone growth through endochondral ossification.

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