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1.
Mol Cell ; 82(13): 2443-2457.e7, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35613620

RESUMO

RAF protein kinases are effectors of the GTP-bound form of small guanosine triphosphatase RAS and function by phosphorylating MEK. We showed here that the expression of ARAF activated RAS in a kinase-independent manner. Binding of ARAF to RAS displaced the GTPase-activating protein NF1 and antagonized NF1-mediated inhibition of RAS. This reduced ERK-dependent inhibition of RAS and increased RAS-GTP. By this mechanism, ARAF regulated the duration and consequences of RTK-induced RAS activation and supported the RAS output of RTK-dependent tumor cells. In human lung cancers with EGFR mutation, amplification of ARAF was associated with acquired resistance to EGFR inhibitors, which was overcome by combining EGFR inhibitors with an inhibitor of the protein tyrosine phosphatase SHP2 to enhance inhibition of nucleotide exchange and RAS activation.


Assuntos
Neurofibromina 1 , Proteínas Proto-Oncogênicas A-raf , Proteínas Ativadoras de ras GTPase , Receptores ErbB/genética , Receptores ErbB/metabolismo , Guanosina Trifosfato/metabolismo , Humanos , Neurofibromina 1/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas A-raf/metabolismo , Transdução de Sinais , Proteínas Ativadoras de ras GTPase/metabolismo
2.
Cell Mol Biol (Noisy-le-grand) ; 70(2): 44-50, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38430041

RESUMO

Molecular pathology and clinical characteristics play a crucial role in guiding treatment selection and predicting the prognosis of diffuse large B-cell lymphoma (DLBCL). The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), have emerged as pivotal regulators of immune checkpoints in cancer. The objectives of this study are to investigate the correlation between the expression levels of PD-1 and soluble PD-L1 (sPD-L1) in the peripheral blood of DLBCL patients, analyze their clinicopathological characteristics, and identify the optimal beneficiary group for PD-1/PD-L1 blockade. Peripheral blood samples were collected from 36 DLBCL patients before their initial treatment at Shandong Cancer Hospital between December 2018 and July 2019. The expression levels of PD-1 and sPD-L1 were measured using flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The clinicopathological characteristics, including age, sex, Ann Arbor stage, International Prognostic Index (IPI) score, response to treatment, etc., were recorded for each patient. The surface expression of PD-1 on peripheral blood T cells was significantly higher in DLBCL patients compared to healthy controls. There was a significant association between elevated PD-1 expression levels and the advanced Ann Arbor stage (P=0.0153) as well as the B group (P=0.0184). Higher sPD-L1 levels were associated with the GCB subtype according to Hans's classification (P=0.0435). The expression levels of PD-1 and sPD-L1 in the peripheral blood of DLBCL patients are significantly correlated with advanced disease stage, B group, and GCB subtype according to Hans's classification. This suggests that the PD-1/PD-L1 axis play a critical role in specific subgroups of DLBCL. Targeting this axis could serve as a potential therapeutic strategy to enhance the clinical outcomes of DLBCL patients. Further studies are necessary to explore the prognostic implications of PD-1 and sPD-L1 expression levels in DLBCL patients.


Assuntos
Antígeno B7-H1 , Linfoma Difuso de Grandes Células B , Humanos , Antígeno B7-H1/genética , Receptor de Morte Celular Programada 1/genética , Linfoma Difuso de Grandes Células B/genética , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo
3.
J Biochem Mol Toxicol ; 38(6): e23734, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38764151

RESUMO

We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.


Assuntos
Autofagia , Curcumina , MicroRNAs , Prolactinoma , MicroRNAs/genética , MicroRNAs/metabolismo , Curcumina/farmacologia , Humanos , Autofagia/efeitos dos fármacos , Prolactinoma/tratamento farmacológico , Prolactinoma/patologia , Prolactinoma/genética , Prolactinoma/metabolismo , Linhagem Celular Tumoral , Regulação para Cima/efeitos dos fármacos , Masculino , Serina-Treonina Quinases TOR/metabolismo , Feminino , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/metabolismo , Adulto , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Pessoa de Meia-Idade , Ratos
4.
BMC Oral Health ; 24(1): 92, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38229070

RESUMO

BACKGROUND: According to previous research, 2.8% of lesions clinically identified as endodontic pathosis were ultimately diagnosed as non-endodontic periapical lesions via histopathology, and 3.7% of these non-endodontic periapical lesions were malignant neoplasms. Rhabdomyosarcoma, a malignant tumor most commonly observed in children, is uncommon in the oral cavity. CASE PRESENTATION: This is a report of a rare case of embryonal rhabdomyosarcoma in a 41-year-old female, in which the lesion was in the maxillary gingiva. The biopsy reports confirmed the diagnosis of embryonal rhabdomyosarcoma. The wide excision of the tumor, free flap reconstruction, chemotherapy, and radiotherapy were performed. Clinical, radiological, and histopathological and management aspects of the neoplasm were also discussed. CONCLUSIONS: This case report aimed to create awareness that rhabdomyosarcoma is one of the differential diagnoses of periapical lesions.


Assuntos
Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Adulto , Criança , Feminino , Humanos , Rabdomiossarcoma Embrionário/patologia , Gengiva/patologia
5.
Zhongguo Zhong Yao Za Zhi ; 49(1): 62-69, 2024 Jan.
Artigo em Zh | MEDLINE | ID: mdl-38403339

RESUMO

The volatile oils are the effective components of Agastache rugosa, which are stored in the glandular scale. The leaves of pulegone-type A. rugosa were used as materials to observe the leaf morphology of A. rugosa at different growth stages, and the components of volatile oils in gland scales were detected by GC-MS. At the same time, qRT-PCR was used to determine the relative expression of key enzyme genes in the biosynthesis pathway of monoterpenes in volatile oils. The results showed that the density of A. rugosa glandular scale decreased first and then tended to be stable. With the growth of leaves, the relative content of pulegone decreased from 79.26% to 3.94%(89.97%-41.44%), while that of isomenthone increased from 2.43% to 77.87%(0.74%-51.01%), and the changes of other components were relatively insignificant. The correlation analysis between the relative content of monoterpenes and the relative expression levels of their key enzyme genes showed that there was a significant correlation between the relative content of menthone and isomenthone and the relative expression levels of pulegone reductase(PR)(r>0.6, P<0.01). To sum up, this study revealed the accumulation rules of the main components of the contents of the glandular scale of A. rugosa and the expression rules of the key enzyme genes for biosynthesis, which provided a scientific basis and data support for determining the appropriate harvesting period and quality control of the medicinal herbs. This study also initially revealed the biosynthesis mechanism of the monoterpenes mainly composed of pulegone and isomenthone in A. rugosa, laying a foundation for further research on the molecular mechanism of synthesis and accumulation of monoterpenes in A. rugosa.


Assuntos
Agastache , Monoterpenos Cicloexânicos , Óleos Voláteis , Óleos Voláteis/análise , Agastache/metabolismo , Monoterpenos/metabolismo
6.
Epilepsy Behav ; 138: 109056, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36571868

RESUMO

BACKGROUND: Cognitive behavioral therapy (CBT) is the recommended treatment for depression in patients with epilepsy (PWE). However, there are no studies that calculate the effect size of CBT on depression and quality of life (QoL) in PWE. METHODS: We searched seven electronic databases (PubMed, Web of Science, Embase, Cochrane Library, Clinical Trials, Ovid Medline, and PsycINFO). We included 13 studies examining CBT for depression in PWE and calculated its effect size. RESULTS: A total of 13 studies met the criteria. After treatment, CBT improves depression in PWE (g = 0.36, 95%CI: 0.18 to 0.54, I2 = 50%), and the efficacy maintains during follow-up (g = 0.47, 95%CI: 0.04 to 0.89, I2 = 80%). Subgroup analysis has shown that individual CBT (g = 0.47, 95%CI: 0.20 to 0.73, I2 = 0%) had a greater effect size than group CBT (g = 0.30, 95%CI: 0.07 to 0.53, I2 = 62%) in the treatment of depression. Likewise, CBT has a positive effect on the QoL improvement of PWE (g = 0.34, 95%CI: 0.11 to 0.57, I2 = 64%). In controlling seizures, CBT did not differ from the control group (g = -0.06, 95%CI: -0.32 to 0.19, I2 = 0%). CONCLUSIONS: Cognitive behavioral therapy interventions were effective in improving depression and QoL in PWE, but not effective in controlling seizures. The efficacy of CBT interventions targeting seizure control seems to be uncertain.


Assuntos
Terapia Cognitivo-Comportamental , Epilepsia , Humanos , Depressão/etiologia , Depressão/terapia , Qualidade de Vida , Epilepsia/complicações , Epilepsia/terapia , Convulsões
7.
Neuroradiology ; 65(10): 1483-1495, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37608218

RESUMO

PURPOSE: The aim of this study was to investigate alterations in the topological organization of whole-brain functional networks in patients with chronic low back pain (CLBP) and characterize the relationship of these alterations with pain characteristics. METHODS: Thirty-three CLBP patients and 34 matched healthy controls (HCs) underwent fMRI scans. A graph-theoretical approach was applied to identify brain network changes in patients suffering from chronic low back pain given its nonspecific etiology and complexity. Graph theory-based analysis was used to construct functional connectivity matrices and extract the features of small-world networks of the brain in both groups. Then, the whole-brain functional connectivity differences were characterized by network-based statistics (NBS) analysis, and the relationship between the altered brain features and clinical measures was explored. RESULTS: At the global level, patients with CLBP showed significantly decreased gamma, sigma, global efficiency, and local efficiency and increased lambda and shortest path length compared with HCs. At the regional level, there were deficits in nodal efficiency within the default mode network and salience network. NBS analysis demonstrated that decreased functional connectivity was present in the CLBP patients, mainly in the frontolimbic circuit and temporal regions. Furthermore, aspects of topological dysfunctions in CLBP were correlated with pain severity. CONCLUSION: This study highlighted the aberrant topological organization of functional brain networks in CLBP, which may shed light on the pathophysiology of CLBP and support the development of pain management approaches.


Assuntos
Dor Lombar , Humanos , Dor Lombar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Lobo Temporal
8.
Cryobiology ; 113: 104586, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37722470

RESUMO

In order to make dry ice transportation of vitrified embryos practical, a near-equilibrium vitrification was developed using a cryoprotectant solution (EDFS10/10a), by which mouse embryos at various stages were vitrified in a near-equilibrium environment. EDFS10/10a consisted of 10% (v/v) ethylene glycol, 10% (v/v) Me2SO, 0.4 M sucrose and 24% (w/v) Ficoll PM70. This method exhibited the benefits of slow freezing and vitrification, with a low risk of osmotic injury. In this study, we investigated whether mouse oocytes are vitrifiable with EDFS10/10a in a highly dehydrated/concentrated state, and whether they can remain fertilizable and developing into embryos after vitrification. When mature mouse oocytes were vitrified in liquid nitrogen and after 4-28 days of storage at -80 °C, high survival rates were observed (88-99%). Vitrified and warmed oocytes were subjected to partial zona dissection and in vitro fertilized. The rate of 2-cell stage was 80-82%. Blastocyst formation rate was 55-70% which was similar to that of embryos derived from fresh oocytes. After the 2-cell embryos were transferred to recipient mice, the implantation and offspring rates did not differ significantly from those of embryos derived from fresh oocytes, indicating that vitrified oocytes retained the developmental ability. Therefore, it is possible to vitrify mouse oocytes in a near-equilibrium state using EDFS10/10a and conveniently transported using dry ice.


Assuntos
Criopreservação , Vitrificação , Camundongos , Animais , Criopreservação/métodos , Gelo-Seco , Crioprotetores/farmacologia , Oócitos , Blastocisto
9.
J Plant Res ; 136(1): 33-45, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36471197

RESUMO

Floral organ movements that ensure autonomous selfing are likely to occur in species that grow in habitats with pollinator scarcity and/or an unpredictable environment. Stamen curvature and temporal flower closure are two important floral behaviors that can influence plant pollination mode and reproductive success. However, both behaviors are rarely reported within a species, and little is known about how these two movements of floral organs ensure reproductive success in an unpredictable early spring environment with few pollinators. The aim of this study was to assess whether stamen curvature and temporal flower closure ensure successful reproduction of Leontice incerta in its cold desert habitat. Flowering phenology, floral traits, stamen curvature patterns and flower visitors were surveyed. The breeding system, capacity and timing for autonomous selfing were estimated by pollination manipulations. The timing of floral opening and closure, and benefits of temporal flower closure were determined. We found that flowering of L. incerta began in late March to early April in two populations in two years, and the yellow flowers had neither nectar nor scent. Floral visitation occurred very rarely, but bees (Colletes sp.) were potential pollinators. Fruit and seed set of open and bagged flowers did not differ significantly from that of self-pollinated or cross-pollinated flowers. However, removal of stamens significantly decreased seed set. Self-pollination occurs when the stamens curve and anthers touch the stigma autonomously, suggesting autonomous selfing assurance of seed production in this self-compatible species. Both fruit and seed set of flowers that were prevented from closing were significantly lower than those of control flowers and closed flowers treated with simulated rain treatment. Therefore, stamen curvature and temporal floral closure can ensure successful sexual reproduction of L. incerta in early spring in the cold desert, where lack of pollinators otherwise may lead to pollination failure.


Assuntos
Polinização , Reprodução , Animais , Abelhas , Flores , Néctar de Plantas , Ásia
10.
J Environ Manage ; 344: 118611, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37453301

RESUMO

Polychlorinated dibenzo-p-dioxin/furans (PCDD/F) have a great threat to the environment and human health, resulting in controlling PCDD/F emissions to regulation far important for emission source. Considering 2,3,4,7,8-pentachlorodibenzo-p-furan (PeCDF) identified as the most contributor to international toxic equivalent, 2,3,4,7,8-PeCDF can be considered as the target molecule for the adsorption of PCDD/F emission from industries. With the aim to in-depth elucidate how different types of nitrogen (N) species enhance 2,3,4,7,8-PeCDF on the biochar and guide the specific carbon materials design for industries, systematic computational investigations by density functional theory calculations were conducted. The results indicate pristine biochar intrinsically interacts with 2,3,4,7,8-PeCDF by π-π electron donor and acceptor (EDA) interaction, six-membered carbon rings of PeCDF parallel to the biochar surface as the strongest adsorption configuration. Moreover, by comparison of adsorption energy (-150.16 kJ mol-1) and interaction distance (3.593 Å) of pristine biochar, environment friendly N doping can enhance the adsorption of 2,3,4,7,8-PeCDF on biochar. Compared with graphitic N doping and pyridinic N doping, pyrrolic N doping biochar presents the strongest interaction toward 2,3,4,7,8-PeCDF molecule due to the highest adsorption energy (-155.56 kJ mol-1) and shortest interaction distance (3.532 Å). Specially, the enhancing adsorption of PeCDF over N doped biochar attributes to the enhancing π-π electron EDA interaction and electrostatic interaction. In addition, the effect of N doping species on PeCDF adsorbed on the biochar is more than that of N doping content. Specially, the adsorption capacity of N doping biochar for PCDD/F can be improved by adding pyrrolic N group most efficiently. Furthermore, pyrrolic N and pyridinic N doping result in the entropy increase, and electrons transform from pyrrolic N and pyridinic N doped biochar to 2,3,4,7,8-PeCDF molecule. A complete understanding of the research would supply crucial information for applying N-doped biochar to effectively remove PCDD/F for industries.


Assuntos
Nitrogênio , Dibenzodioxinas Policloradas , Humanos , Adsorção , Carbono
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(10): 1296-1300, 2023 Oct 10.
Artigo em Zh | MEDLINE | ID: mdl-37730235

RESUMO

OBJECTIVE: To delineate the origin and content of a mosaicism small supernumerary marker chromosome (sSMC) in a fetus with combined chromosomal karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH). METHODS: The fetus of a 31-year-old pregnant woman who had presented at the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City in 2022 was selected as the study subject. Non-invasive prenatal testing suggested that the fetus has harbored a 8.75 Mb duplication in 4q12q13.1. With informed consent, amniotic fluid and peripheral blood samples were taken from the couple for chromosomal karyotyping analysis. The origin and content of a sSMC was identified by CMA, and its proportion in amniotic fluid was determined with a FISH assay. RESULTS: The karyotypes of the pregnant woman, her husband and the fetus were respectively determined as 46,XX, 46,XY,inv(9)(p12q12), and 47,XY,inv(9)(p12q12)pat,+mar[75]/ 46,XY,inv(9)(p12q12)pat[25]. CMA test of the amniotic fluid sample was arr[hg19]4p11q13.1(48978053_63145931)×3, which revealed no mosaicism. However, FISH analysis showed that 59% of interphase cells from the cultured amniotic fluid sample had contained three signals for the centromere of chromosome 4, whilst 65% of interphase cells from the re-sampled amniotic fluid had three such signals, which confirmed the existence of trisomy 8 mosaicism. CONCLUSION: Chromosomal structural abnormality combined with mosaicism can be delineated with combined chromosomal karyotyping and molecular techniques such as FISH and CMA, which has enabled more accurate counseling for the family.


Assuntos
Técnicas Genéticas , Mosaicismo , Humanos , Criança , Feminino , Gravidez , Adulto , Hibridização in Situ Fluorescente , Líquido Amniótico , Cromossomos Humanos Par 4
12.
Int Microbiol ; 25(4): 723-732, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35725861

RESUMO

BACKGROUND/AIMS: The aim was to characterize a bacterium causing intestinal mucosal barrier damage and to identify the possible invasion mechanism. MATERIALS AND METHODS: The intestinal permeability and tight junction protein levels were detected in guinea pigs infected with Escherichia coli D-09 via immunofluorescence analysis and western blotting. In order to explain this invasion mechanism at the gene level, whole genome sequencing analysis was performed on this bacterium. RESULTS: The results showed an increased intestinal permeability and upregulated expression of the leaky protein claudin-2 in both the colon and liver of the infected animals. In addition, the draft genome of E. coli D-09 comprised 42 scaffolds (size, > 645 bp) with a total size of 4,679,567 bp. A total of 4379 protein coding genes were identified, which contained 45 antibiotic resistance and 86 virulence-related genes and covered 88.0% of the whole genome. CONCLUSIONS: This study verified that the human-derived enteroinvasive E. coli strain could destroy intestinal barrier function in guinea pigs. Additionally, our data first characterized the genome features of E. coli O124:K72 D-09, which may provide new insights into the possible invasion mechanism.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Animais , Claudina-2/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Cobaias , Humanos , Intestinos/microbiologia , Proteínas de Junções Íntimas/metabolismo
13.
Environ Res ; 208: 112761, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35065932

RESUMO

As a highly contagious disease, COVID-19 caused a worldwide pandemic and it is still ongoing. However, the infection in China has been successfully controlled although its initial transmission was also nationwide and has caused a serious public health crisis. The analysis on the early-stage COVID-19 transmission in China is worth investigating for its guiding significance on prevention to other countries and regions. In this study, we conducted the experiments from the perspectives of COVID-19 occurrence and intensity. We eliminated unimportant factors from 113 variables and applied four machine learning-based classification and regression models to predict COVID-19 occurrence and intensity, respectively. The influence of each important factor was analysed when applicable. Our optimal model on COVID-19 occurrence prediction presented an accuracy of 91.91% and the best R2 of intensity prediction reached 0.778. Linear regression-based model was identified as unable to fit and predict the intensity, and thus only the variable influence on COVID-19 occurrence can be explained. We found that (1) CO VID-19 was more likely to occur in prosperous cities closer to the epicentre and located on higher altitudes, (2) and the occurrence was higher under extreme weather and high minimum relative humidity. (3) Most air pollutants increased the risk of COVID-19 occurrence except NO2 and O3, and there existed a lag effect of 6-7 days. (4) NPIs (non-pharmaceutical interventions) did not show apparent effect until two weeks after.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Poluentes Atmosféricos/análise , Poluição do Ar/análise , COVID-19/epidemiologia , China/epidemiologia , Cidades , Humanos , Aprendizado de Máquina , Material Particulado/análise , SARS-CoV-2 , Fatores Sociais
14.
Exp Cell Res ; 395(1): 112176, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682784

RESUMO

As a kind of high-incidence malignant tumors in the digestive tract, colorectal cancer (CRC) has extremely morbidity and mortality in the population. LncRNAs have been proved to regulate the proliferation, chemoresistance and metastasis of tumors including CRC. LINC00689 and miR-31-5p in CRC were found misregulated in CRC by TCGA analysis. However, the mechanism of LINC00689 and miR-31-5p in regulating CRC remains unknown. The expression levels of LINC00689, miR-31-5p and LATS2 in CRC tissues and cell lines were examined by qRT-PCR assay. Cell proliferation, metastasis (including invasion and migration) were quantified by MTT assay, colony formation and Transwell assay, respectively. Western blotting assay was then performed to verify the levels of YAP/ß-catenin and metastasis-related proteins. Dual-luciferase reporter assay and RIP assay were performed to evaluate the interaction between LINC00689 (LATS2) and miR-31-5p. Moreover, the function of LINC00689 and miR-31-5p were confirmed by CRC xenograft in nude mice. LINC00689 was decreased while miR-31-5p was increased in CRC. The overexpression of LINC00689 or the knockdown of miR-31-5p inhibited cell proliferation, chemoresistance and metastasis of CRC cells. Meanwhile, the up-regulated LATS2 suppressed the activity of YAP/ß-catenin pathway to repress CRC occurrence. Silencing LATS2 reversed the inhibition effects of overexpression of LINC00689 or knockdown of miR-31-5p on proliferation, chemoresistance and metastasis of CRC cells. LINC00689 indeed acted as a miR-31-5p sponge to inhibit CRC proliferation, chemoresistance and metastasis through up-regulating LATS2 and repressing YAP/ß-catenin signaling pathway.


Assuntos
Proliferação de Células/genética , Neoplasias do Colo/genética , Neoplasias Colorretais/patologia , Metástase Neoplásica/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo
15.
Cryobiology ; 98: 127-133, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33285110

RESUMO

Previously, we developed a method for vitrification of mouse embryos in a near-equilibrium state using EFS35c, PB1 medium containing 35% (v/v) ethylene glycol, and 0.98 M sucrose. This method has advantages in both slow freezing and vitrification. However, since the vitrification solution in this method contains high concentrations of cryoprotectants and thus has high osmolality, the solution would injure oocytes and embryos with high sensitivity to chemical toxicity and high osmolality. In this study, we examined whether embryos could be vitrified in a near-equilibrium state using a solution containing low concentrations of cryoprotectants and thus with low osmolality. To investigate whether embryos were vitrified in a near-equilibrium state, 2-cell mouse embryos were vitrified with EDFS10/10a, PB1 medium containing 10% (v/v) ethylene glycol, 10% (v/v) DMSO, and 0.4 M sucrose, in liquid nitrogen, stored at -80 °C for 4-28 days, and warmed in water at 25 °C. The viability of the embryos was evaluated by the appearance of embryos after warming and developmental ability. When embryos were vitrified in liquid nitrogen using EDFS10/10a, the survival and developmental ability into blastocysts after storage at -80 °C for 7 days were high, indicating that embryos were vitrified in a near-equilibrium state. A high proportion of embryos vitrified with EDFS10/10a developed to term after transportation with dry ice, re-cooling in liquid nitrogen, and transfer to recipients. Therefore, new equilibrium vitrification developed in this study may be useful for oocytes and embryos that are highly sensitive to the toxicity of cryoprotectants and high osmolality.


Assuntos
Criopreservação , Vitrificação , Animais , Blastocisto , Criopreservação/métodos , Crioprotetores/toxicidade , Etilenoglicol/toxicidade , Camundongos
16.
J Reprod Dev ; 67(2): 109-114, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33563870

RESUMO

We previously developed a new vitrification method (equilibrium vitrification) by which two-cell mouse embryos can be vitrified in liquid nitrogen in a highly dehydrated/concentrated state using low concentrations of cryoprotectants. In the present study, we examined whether this method is effective for mouse embryos at multiple developmental stages. Four-cell embryos, eight-cell embryos, morulae, and blastocysts were vitrified with EDFS10/10a, 10% (v/v) ethylene glycol and 10% (v/v) DMSO in FSa solution. The FSa solution was PB1 medium containing 30% (w/v) Ficoll PM-70 plus 0.5 M sucrose. The state of dehydration/concentration was assessed by examining the survival of vitrified embryos after storage at -80°C. When four-cell embryos and eight-cell embryos were vitrified with EDFS10/10a in liquid nitrogen and then stored at -80°C, the survival rate was high, even after 28 days, with relatively high developmental ability. On the other hand, the survival of morulae and blastocysts vitrified in liquid nitrogen and stored at -80°C for four days was low. Therefore, morulae and blastocysts cannot be vitrified in a highly dehydrated/concentrated state using the same method as with two-cell embryos. However, when blastocysts were shrunken artificially before vitrification, survival was high after storage at -80°C for four days with high developmental ability. In conclusion, the equilibrium vitrification method using low concentrations of cryoprotectants, which is effective for two-cell mouse embryos, is also useful for embryos at multiple stages. This method enables the convenient transportation of vitrified embryos using dry ice.


Assuntos
Criopreservação/instrumentação , Crioprotetores/farmacologia , Vitrificação , Animais , Blastocisto/patologia , Blástula/patologia , Sobrevivência Celular , Gelo-Seco , Etilenoglicol/química , Feminino , Ficoll/química , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos ICR , Mórula/patologia , Oócitos/citologia , Concentração Osmolar , Manejo de Espécimes/métodos , Sacarose/química , Temperatura
17.
Medicina (Kaunas) ; 57(12)2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34946328

RESUMO

Cemento-ossifying fibroma (also known as ossifying fibroma or cementifying fibroma) is a benign osteogenic neoplasm. Pain and paresthesia are rarely associated with cemento-ossifying fibroma; thus, nerves must be preserved during excision. With the advent of computer-aided techniques, the use of virtual surgical planning and a customized template can improve the precision of resection and reconstruction, reduce operating time, and improve postoperative outcomes. In this report, we describe a case of cemento-ossifying fibroma in a female patient who underwent segmental mandibulectomy and reconstruction with an iliac bone graft. Additionally, we describe a simple and effective way to preserve the inferior alveolar nerve.


Assuntos
Cementoma , Fibroma Ossificante , Neoplasias Mandibulares , Feminino , Fibroma Ossificante/diagnóstico por imagem , Fibroma Ossificante/cirurgia , Humanos , Remoção , Neoplasias Mandibulares/cirurgia , Nervo Mandibular/cirurgia
18.
Langmuir ; 36(11): 2911-2919, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32115953

RESUMO

Novel luminescent vesicles with enhanced emission were successfully achieved for the first time by an amphiphilic europium complex through its spontaneously self-assembly in an ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([Bmim]PF6). The complex was prepared by europium ions coordinated with terpyridine ligands, which were modified with the hydrophilic ethoxy chains. The enhanced absolute quantum yield and prolonged fluorescence lifetime of complex in vesicles were observed because of the effective shielding of the quench effects caused by both solvent and complex concentration. Compared to the aggregates formed in other solvents, the vesicles obtained in [Bmim]PF6 showed the best luminescence intensity with the quantum efficiency (37.74%) and luminescent emission lifetime (1.915 ms) both increased about 10 times more. Furthermore, this europium complex was designed to show unsaturated coordination, which made the vesicle luminescence easily quenched when contacting with water. The fluorescence sensing of water with this vesicle as probe was therefore possible, where several unique properties like high sensitivity, low detection limit (0.05 vol %), visible color change, and fast response had been observed. Such designed systems are expected to provide strategies to develop novel supramolecular aggregates in ionic liquids and offer guidance for luminescence detection with facile and wide applications.

19.
Soft Matter ; 16(5): 1170-1178, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31934710

RESUMO

Multicolored photoluminescence induced by UV irradiation in soft materials has invaluable potential in display and detection applications. Here, an ionic liquid (ethylammonium nitrate, EAN)-mediated luminescent lyotropic liquid crystal (LLC) has been fabricated, where an europium complex with two ligands (Eu(DBM)3BQ, DBM = dibenzoylmethane and BQ = 2,2'-biquinoline) was doped. The obtained LLC exhibited enhanced fluorescence intensity and lifetime compared to those of Eu(DBM)3BQ in EAN solution. Interestingly, the luminescent LLC color from the initial red emission of the complex was changed gradually to green when the UV exposure was extended. Though the DBM ligand displayed the typical photo-degradation, the emission intensity of BQ increased drastically. A mechanism based on an UV-induced trans-to-cis isomerization of BQ was proposed to explain such an unusual luminescence phenomenon. Both the experimental and computational results indicated an intra ligand charge transfer (ILCT) accompanied with the BQ isomerization under continuous UV irradiation, which resulted in the enhanced green light emission. The results obtained here are referable for better understanding the interplay between weak interactions and modulation of novel lanthanide-based photochromism systems under UV exposure.

20.
Pharmacol Res ; 148: 104461, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31542404

RESUMO

Intestinal epithelial barrier dysfunction is a key pathology of colitis. Autophagy of epithelial cells maintains homeostasis of the intestinal barrier by inhibiting apoptosis and stimulating degradation of the tight junction protein claudin-2. This study investigated the effects and mechanism of activity of sinensetin, a polymethylated flavonoid isolated from tangerine peel and citrus, on intestinal barrier dysfunction in colitis. Animal model of colitis were established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid and oral treatment with dextran sulfate sodium. Epithelial barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in Caco-2 cells, respectively. Epithelial cell autophagy assayed by autophagosome formation and expression of autophagy-related protein. Sinensetin reversed colitis-associated increase in intestinal permeability, significantly promoted epithelial cell autophagy, and further decreased epithelial cell apoptosis, and reduced mucosal claudin-2. Sinenstetin alleviated colitis symptoms rats and mice with colitis. Knockdown of 5' adenosine monophosphate-activated protein kinase (AMPK) reversed the promotion of epithelial autophagy by sinensetin. In conclusion, sinensetin significantly alleviated intestinal barrier dysfunction in colitis by promoting epithelial cell autophagy, and further inhibiting apoptosis and promoting claudin-2 degradation. The results highlighted novel potential benefits of sinensetin in colitis.


Assuntos
Autofagia/efeitos dos fármacos , Colite/tratamento farmacológico , Células Epiteliais/efeitos dos fármacos , Flavonoides/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células CACO-2 , Claudina-2/metabolismo , Colite/metabolismo , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo
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