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1.
J Immunol Res ; 2021: 6203759, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497859

RESUMO

Background: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, which remains a major cause of morbidity and mortality in patients with head and neck cancers. However, the critical immune-related signatures and their prognostic values have rarely been investigated. Materials and Methods: Gene differential analysis was used to measure the differences of gene expression between the groups. Correlation analysis was used to assess the association between the gene expression levels and immune-related risk score/DNA methylation levels. The gene set enrichment analysis (GSEA) was used to identify the pathways or cell types enriched by those identified differentially expressed genes (DEGs). Results: In this study, we identified four immune-related gene signatures, including CTSG, TNFRSF4, LCORL, and PLAU, that were significantly associated with the overall survival in OSCC patients from the Cancer Genome Atlas (TCGA) OSCC cohort. Moreover, these four immune-related signatures were differentially expressed between the OSCC and nontumor tissues. The two groups (high and low risk) stratified by the immune-related risk scores had significantly different OS and mortality rates. The gene expression patterns and prognostic values of these immune-related signatures were also verified in two independent validation cohorts. Furthermore, the downregulated genes in the high-risk group (which were also upregulated in the low-risk group) were significantly enriched in the cell type-specific signatures of type 2 T helper cell (Th2), plasmacytoid dendritic cell (pDC), and memory B cell. In contrast, the upregulated genes in the high-score group were enriched in growth factor receptor-related signaling pathways, such as the VEGFA-VEGFR2 signaling pathway, PI3K-Akt signaling pathway, focal adhesion-PI3K-Akt-mTOR signaling pathway, and PDGF pathway, suggesting that those pathways were inversely correlated with immune cell infiltration. Conclusion: In summary, the immune-related signatures had the potential for predicting the risk of OSCC patients. Moreover, the present study also improved our understanding of the association between the growth factor receptor pathways and immune cell infiltration in OSCC.

2.
J Immunol Res ; 2021: 6149558, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476262

RESUMO

N6-Methyladenosine (m6A) modification is one of the commonest chemical modifications in eukaryotic mRNAs, which has essential effects on mRNA translation, splicing, and stability. Currently, there is a rising concern on the regulatory role of m6A in tumorigenesis. As a known component in the m6A methyltransferase complex, METTL3 (methyltransferase-like 3) plays an essential role in m6A methylation. Till now, the functions of METTL3 in oral squamous cell carcinoma (OSCC) and its relative mechanism remain to be explored. In this research, through the GEPIA database, we found that high METTL3 expression has a correlation with poor prognosis of squamous cell carcinoma of head and neck. qRT-PCR displayed that METTL3 was highly expressed in OSCC cells. Functionally, METTL3 knockdown reduced the invasion, migration, and proliferation competence of OSCC cells and attenuated the activation of CD8+ T cells. In contrast, METTL3 overexpression resulted in opposite results. GEPIA, UALCAN, and SRAMP databases, PCR, western blot, and m6A RNA methylation assay confirmed the m6A modification of PRMT5 and PD-L1 mediated by METTL3. In conclusion, our results displayed that METTL3 intensified the metastasis and proliferation of OSCC by modulating the m6A amounts of PRMT5 and PD-L1, suggesting that METTL3 may be a therapeutic target for OSCC patients.

3.
Biomed Res Int ; 2021: 3445970, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458365

RESUMO

Mounting evidence has recently shown that role of long noncoding RNA is critical in many human cancers. lncRNA GSTM3TV2 was first proven to play a vital role in pancreatic cancer. However, the mechanism of lncRNA GSTM3TV2 in hepatocellular carcinoma (HCC) is still uncovered. Here, we object to distinguish the expression of lncRNA GSTM3TV2 and reveal its mechanistic relationship with HCC. We observed that the expression of lncRNA GSTM3TV2 and FOSL2 were upregulated in HCC. Knockdown of lncRNA GSTM3TV2 significantly inhibited cell proliferation. Meanwhile, the migration and invasion of HCC cells were greatly decreased by the downregulated lncRNA GSTM3TV2. The luciferase reporter assays showed that lncRNA GSTM3TV2 could be directly bound to miR-597, and the level of miR-597 was also decreased in the tumor tissues. lncRNA GSTM3TV2 could stabilize FOSL2 expression, resulting in the oncogenic properties of lncRNA GSTM3TV2 in HCC. Our study indicated the oncogenic activities of lncRNA GSTM3TV2 and emphasized the role of the miR-597/FOSL2 signaling pathway.


Assuntos
Carcinoma Hepatocelular/metabolismo , Antígeno 2 Relacionado a Fos/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Feminino , Antígeno 2 Relacionado a Fos/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Transdução de Sinais , Regulação para Cima
4.
Artigo em Inglês | MEDLINE | ID: mdl-34351129

RESUMO

The reactivity of garnet solid electrolytes toward humid air hinders their practical application despite their attractive, superior properties such as high Li+ conductivity and wide electrochemical window. Sealing garnets with organic solvents can not only prevent them from reacting with humid air but also render them compatible with other processing technologies. Therefore, the chemical and structural stability of garnets in organic solvents must be studied. In this study, we selected several commonly used organic solvents with different representative functional groups to investigate their stability with garnets and reaction mechanisms. The experiments and theoretical calculations revealed that all of the solvents reacted with garnets through Li-H exchange, and solvent acidity determined the reaction strength. Furthermore, the solvent acidity was closely correlated to the functional groups connected to H atoms, which can affect charge distribution. Solvents or the tautomer of the solvents with hydroxyl groups such as alcohol, acetone, and N-methyl pyrrolidone, which are relatively more acidic, can lead to a violent reaction with changes in the lattice parameters of garnets. Ether compounds and saturated aliphatic hydrocarbons with relatively low acidity are highly stable against garnets. The proposed reaction mechanisms and rules may help in selecting appropriate solvents for different applications of garnets.

5.
Surgery ; 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34340820

RESUMO

BACKGROUND: Preventing cervical reoperations is important-especially after parathyroidectomy. We sought to examine early predictors of recurrence of primary hyperparathyroidism after surgical cure. METHODS: Adult patients with sporadic primary hyperparathyroidism treated with parathyroidectomy between September 1, 1997, and September 1, 2019, with confirmed eucalcemia at 6 months postoperatively were identified. Recurrence was defined as hypercalcemia (>10.2 mg/dL) with an elevated or nonsuppressed parathyroid hormone level on subsequent follow-up. RESULTS: Parathyroidectomy was performed in 522 patients (median age, 62.1 years, 77% female) with the majority undergoing planned minimally invasive parathyroidectomy (85.4%, n = 446). After a median follow-up of 30.9 months, 13 patients (2.5%) recurred (median time to recurrence 50.2 months, interquartile range 27.9-66.5), all of whom underwent planned minimally invasive parathyroidectomy (n = 13/446, 2.9%). Recurrence was more common in those with higher (but still normal) 6-month calcium (10.1 vs 9.3 mg/dL, P < .001) or parathyroid hormone values (64 vs 46 pg/mL, P < .01). Multivariate analysis revealed that age >66.5 years, calcium ≥9.8mg/dL and parathyroid hormone ≥80 pg/mL at 6 months were associated with increased risk of recurrence. In addition, the presence of at least 1 preoperative imaging study that conflicted with intraoperative findings among minimally invasive parathyroidectomy patients (n = 446) was associated with increased risk of recurrence (hazard ratio 4.93, 95% confidence interval 1.25-16.53, P = .016). CONCLUSION: Recurrence of sporadic primary hyperparathyroidism after initial surgical cure in the era of minimally invasive parathyroidectomy is 2.5%. Identification of those at risk for recurrence using 6-month serum calcium ≥9.8 mg/dL, parathyroid hormone ≥80 pg/mL, and/or potentially conflicting localization studies may inform surveillance strategies.

6.
J Immunol Res ; 2021: 1830790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34355042

RESUMO

LINC01355 has been demonstrated to be dysregulated in several cancers. However, the exact molecular function of LINC01355 in the pathogenesis of OSCC remains unstudied. Here, we reported the effect of LINC01355 in OSCC and investigated the mechanisms. Firstly, we found that the results indicated LINC01355 was increased in OSCC cells. Knockdown of LINC01355 repressed OSCC cell proliferation, migration, and invasion. Recently, immunotherapy is a significant method for the treatment of cancers, in which CD8+ T cells exhibit a significant role. The influence of LINC01355 on the antitumor activity of CD8+ T cells was also focused in this study. As shown, the silence of LINC01355 could repress OSCC tumor growth via inducing CD8+ T cell immune responses. In addition, we found that downregulation of LINC01355 significantly restrained CD8+ T cell apoptosis, induced CD8+ T cell percentage, and enhanced the cytolysis activity when cocultured with OSCC cells. It has been reported that the Notch pathway represses CD8+ T cell activity in cancer patients. In our present study, we displayed that lack of LINC01355 suppressed OSCC malignant behaviors and enhanced the antitumor activity of CD8+ T cells via inactivating Notch signaling. We showed that decreased LINC01355 significantly restrained the Notch signal via a decrease of Notch-1, JAG-1, and HES-1. Repression of Notch1 reversed the effect of LINC01355 in OSCC cells. In conclusion, it was implied that LINC01355 might induce the development of OSCC via modulating the Notch signal pathway, which could provide a candidate therapeutic target for OSCC.

7.
J Immunol Res ; 2021: 5524231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414241

RESUMO

lncRNAs are related to the progression of various diseases, including oral squamous cell carcinoma (OSCC), which is a common squamous cell carcinoma of the head and neck. Tumor-associated macrophages and tumor cells are significant components of tumor microenvironment. M2 polarization of tumor-associated macrophages is a crucial actor in tumor malignancy and metastasis. In this study, we studied the molecular mechanism of lncRNA DCST1-AS1 in OSCC. Here, we reported that DCST1-AS1 was significantly increased in OSCC cells. We found that loss of DCST1-AS1 obviously inhibited the proliferation, migration, and invasion of OSCC cells and xenograft tumor growth. Meanwhile, silencing of DCST1-AS1 also repressed the percentage of macrophages expressing M2 markers CD206 and CD11b. DCST1-AS1 shRNA enhanced the percentage of macrophages expressing M1 markers CD80 and CD11c. Then, we observed that loss of DCST1-AS1 suppressed OSCC progression via inactivating NF-κB signaling. As well established, NF-κB signaling exerts critical roles in tumor progression, and our study proved that DCST1-AS1 could regulate NF-κB signaling. We proved that blocking the NF-κB pathway using antagonists greatly downregulated OSCC progression and M2 macrophage polarization induced by the overexpression of DCST1-AS1. To sum up, we reported that DCST1-AS1 plays an important role in modulating OSCC tumorigenicity and M2 macrophage polarization through regulating the NF-κB pathway.

8.
Neoplasma ; 68(5): 965-974, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34196215

RESUMO

Notably, a growing number of long noncoding RNAs (lncRNAs) have been recognized to play critical roles in hepatocellular carcinoma (HCC) progression. In this study, we identified a new lncRNA, Linc1749808 (ID: XR_001749808.1) based on microarray data from HCC tissues. Linc1749808 levels in 72 HCC tissues and paracancerous samples were detected by qRT-PCR. The interaction between Linc1749808 and microRNA-206 (miR-206) was assessed by bioinformatic analysis and luciferase assays. Linc1749808 depletion assays, Transwell assays, and miR-206-inhibitor rescue experiments were performed to examine the role of the Linc1749808/miR-206 axis in HCC cells. Our results showed that Linc1749808 was highly expressed in both HCC tissues and cell lines. Linc1749808 expression was significantly correlated with microvascular invasion, metastasis, and prognosis. After the knockdown of Linc1749808, the metastatic potential of 97H and HepG2 cells was attenuated in vitro and in vivo, but the proliferative capacity did not significantly change. Furthermore, Linc1749808 was found to act as a sponge of miR-206. Inhibition of miR-206 counteracted the effect of Linc1749808 knockdown in 97H cells by regulating YAP1 and epithelial-mesenchymal transition (EMT). In summary, these findings show that Linc1749808 can exacerbate the metastasis of HCC by sponging miR-206.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética
9.
Biochem Biophys Res Commun ; 566: 108-114, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34119822

RESUMO

Circular RNAs (circRNAs) have been widely reported to participate in progression of various cancers, including oral cancer. Previous study showed circ_0001461 was aberrantly expressed in oral squamous cell carcinoma (OSCC), while its role in tumorigenesis of OSCC remains largely unclear. In this study, we confirmed that circ_0001461 was highly expressed in OSCC cell lines and tumor tissues. Knocking down of circ_0001461 suppressed cell proliferation, migration and invasion in vitro, and repress xenograft tumor growth in vivo. Mechanistically, we found circ_0001461 regulates OSCC cell proliferation, migration and invasion through sponging miR-145. Furthermore, circ_0001461 promotes the resistance of TNF-α-induced apoptosis of OSCC cells by modulating miR-145/TLR4/NF-κB pathway. In general, our study demonstrated a novel regulatory mechanism that circ_0001461/miR-145/TLR4/NF-κB axis modulates oral squamous cell carcinoma progression.

10.
J Cell Mol Med ; 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34117688

RESUMO

Oral squamous cell carcinoma (OSCC) is a pathological type of oral cancer, which accounts for over 90% of oral cancers. It has been widely shown that circRNA is involved in the regulation of multiple malignant oral diseases including OSCC. However, the mechanism underlying how circRNA regulates OSCC is still not clearly elucidated. In this article, we report circFOXO3 promotes tumor growth and invasion of OSCC by targeting miR-214 which specifically degrades the lysine demethylase 2A (KDM2A). CircRNA sequencing was conducted in OSCC tumor and tumor-side tissues, and the expression of circFOXO3 is found to be markedly increased in tumor tissues. CircFOXO3 is also highly expressed in several OSCC cell lines compared with human oral keratinocytes. Transwell assay and colony formation showed that knockdown of circFOXO3 prevents the invasion and proliferation of oral cancer cells. Via bioinformatic research, miR-214 was found to be the target of circFOXO3 and correlate well with circFOXO3 both in vitro and in vivo. KDM2A was then validated by database analysis and luciferase assay to be the direct target of miR-214. KDM2A helps to promote tumor invasiveness and proliferation of OSCC. Collectively, our results proved that circFOXO3 sponges miR-214 to up-regulate the expression of KDM2A, thus promotes tumor progression in OSCC.

11.
World J Surg Oncol ; 19(1): 101, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827601

RESUMO

BACKGROUND: Laparoscopic gastrectomy is an acceptable procedure for early-stage gastric cancer; however, most patients are diagnosed at an advanced stage and older age in Taiwan. The feasibility and safety of applying laparoscopic gastrectomy in daily practice remain unclear. This study aimed to examine the short- and long-term outcomes of laparoscopic gastrectomy versus open procedures. METHODS: From 2007 to 2015, 192 patients who underwent open gastrectomy and 189 patients who underwent laparoscopic gastrectomy for gastric cancer at a single center were included. Propensity score matching analysis was used to adjust selection biases associated with age, preoperative hemoglobin, the extent of resection, tumor size, and stage of the disease. The demographics, perioperative parameters, short-term postoperative results, and 5-year survival data were analyzed. RESULTS: Open gastrectomy was more frequently performed in the elderly, larger tumor size, advanced stage of the disease, and disease requiring total gastrectomy or combined organ resection. After propensity score matching, 108 patients with laparoscopic gastrectomy were compared to 108 patients with open gastrectomy. The morbidity rates were not different in both groups (25.9%), while hospital stay was shorter in the laparoscopic group (16.0 vs. 18.8 days, p = 0.04). The 5-year overall survival and disease-free survival were superior in the laparoscopic group (p = 0.03 and p = 0.01, respectively); however, the survival differences were not significant in the subgroup analysis by stage. Laparoscopic gastrectomy had fewer recurrences than open gastrectomy. The pattern of recurrence was not different between the groups. CONCLUSIONS: Laparoscopic gastrectomy can be safely applied in both early and locally advanced gastric cancer without compromising oncologic outcomes. TRIAL REGISTRATION: Retrospective registration.


Assuntos
Laparoscopia , Neoplasias Gástricas , Idoso , Gastrectomia/efeitos adversos , Humanos , Tempo de Internação , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Pontuação de Propensão , Neoplasias Gástricas/cirurgia , Taiwan , Resultado do Tratamento
12.
Biol Psychol ; 161: 108083, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33774133

RESUMO

Dual-processing theory assumes recognition memory involves two distinct processes: familiarity and recollection. Although the influence of emotional intensity on memory has been investigated, it remains unclear whether the influence of negative stimuli depends on familiarity or recollection. This study recorded event-related potentials as participants performed a modified remember/know procedure with highly negative, mildly negative, and neutral stimuli. The results showed that, relative to highly negative stimuli, mildly negative and neutral stimuli showed increased mean discrimination for responses of 'know' in the following pattern: highly negative < mildly negative < neutral. Neutral stimuli enhanced the frontal old/new effect. Relative to mildly negative and neutral stimuli, highly negative stimuli showed increased mean discrimination for responses of 'remember', and enhanced the parietal old/new effect. These results suggested negative emotional intensity influences recollection and familiarity differently, as recognition of highly negative stimuli depends on recollection, and recognition of neutral stimuli depends on familiarity.


Assuntos
Eletroencefalografia , Reconhecimento Psicológico , Emoções , Potenciais Evocados , Humanos , Rememoração Mental
13.
Int J Biol Sci ; 17(3): 768-780, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767587

RESUMO

Long noncoding RNAs (LncRNAs) are emerging as crucial regulators in the pathophysiological process of various tumors, including HCC. Here, we identify a novel lncRNA Linc-KILH (KRT19 interacting long noncoding RNA in hepatocellular carcinoma), which is significantly up-regulated in HCC tissues and positively correlated with larger tumor size, severer microvascular invasion, more intrahepatic metastasis and decreased survival of HCC patients. Silence of Linc-KILH remarkably inhibited the proliferation and metastasis abilities of KRT19-positive HCC cells in vitro and in vivo. Mechanistically, Linc-KILH interacts with KRT19 and then inhibits the phosphorylation of KRT19 on Ser35, thereby, enhancing the translocation of KRT19 from cytoplasm to membrane in KRT19 positive HCC cells. Additionally, we validated that KRT19 interacts with ß-catenin but not RAC1 in HCC cells. Linc-KILH enhanced the interaction between ß-catenin and KRT19 in cytoplasm and promoted the nuclear translocation of ß-catenin in HCC cells. Furthermore, Linc-KILH could enhance the promoting function of KRT19 on Notch1 signaling with the existence of KRT19 in HCC cells. Collectively, we revealed that Linc-KILH exerts a vital function in KRT19 positive HCC progression and may likely be developed into an effective therapeutic target for HCC.

14.
Dermatology ; 237(4): 579-587, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33582672

RESUMO

BACKGROUND: There are great interindividual variations in the clinical efficacy of methotrexate (MTX) treatment and patients' genetic background seems promising in its explanation. OBJECTIVES: The study aimed to test whether the polymorphism of annexin A6 (ANxA6) gene, a susceptibility factor for psoriasis, was associated with the clinical response to MTX therapy. METHODS: A total of 325 patients enrolled in the study received oral MTX treatment, of whom 310 completed the 1-year study and performed the genotype analysis. They were defined as responders (a reduction of Psoriasis Area and Severity Index [PASI] score ≥75%) and nonresponders (a reduction of PASI <50%) compared to baseline after 12 weeks of short-time therapy. On 1-year treatment, they were defined as responders if they achieved PASI75 and absolute PASI ≤3, otherwise as nonresponders. The genotypes of 4 single-nucleotide polymorphisms (SNPs) in the ANxA6 gene were verified using the Sequenom platform. Potential predictors associated with the treatment outcome of MTX were assessed by binary logistic regression. RESULTS: We found significant associations for the ANxA6 SNPs of rs11960458, rs960709, and rs13168551 with psoriasis severity. Patients with rs11960458 CC genotype and rs960709 GG genotype showed higher percentages of PASI75 and improvement rates of PASI at 12 weeks. And on 1-year treatment, statistical difference occurred in rs11960458 rather than other SNPs compared between responders and nonresponders that the frequency of CC genotype was higher in responders (p = 0.019). After adjustment for potential confounders, patients with rs11960458 TT/CT genotype (at 12 weeks: OR 0.483, 95% CI 0.245-0.951, p = 0.035; at 1 year: OR 0.483, 95% CI 0.280-0.833, p = 0.009) were significantly more likely to not respond to MTX both on the short-term and long-term treatment, while rs960709 and rs13168551 polymorphisms were only associated with the short-term efficacy of MTX (p = 0.018 and p = 0.036, respectively). CONCLUSIONS: The CC ge-notype of ANxA6 (rs11960458) was significantly associated with a better response when compared to those patients with the TT/CT genotype, thus being a potential predictor for the clinical efficacy of MTX.

15.
Surgery ; 169(1): 175-184, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32703679

RESUMO

BACKGROUND: It is unclear whether genotype-negative clinical multiple endocrine neoplasia type 1 patients derive equal benefit from prospective surveillance as genotype-positive patients. METHODS: In this retrospective cohort study, we compared genotype-negative patients with clinical multiple endocrine neoplasia type 1 with genotype-positive index cases. Primary outcome was age-related penetrance of manifestations; secondary outcomes were disease-specific survival and clinical course of endocrine tumors. RESULTS: We included 39 genotype-negative patients with clinical multiple endocrine neoplasia type 1 (Male: 33%) and 63 genotype-positive multiple endocrine neoplasia type 1 index cases (Male: 59%). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were 65 years old at last follow-up; genotype-positive multiple endocrine neoplasia type 1 index cases were 50 (P < .001). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were significantly older at their first and second primary manifestation. Only 1 developed a third primary manifestation. No genotype-negative patients with clinical multiple endocrine neoplasia type 1 with primary hyperparathyroidism and a pituitary adenoma developed a duodenopancreatic neuroendocrine tumor. Disease-specific survival was significantly better in genotype-negative patients with clinical multiple endocrine neoplasia type 1. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, primary hyperparathyroidism was single-gland disease in 47% of parathyroidectomies versus 0% in genotype-positive multiple endocrine neoplasia type 1 index cases. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, 17% of duodenopancreatic neuroendocrine tumors were multifocal versus 68% in genotype-positive multiple endocrine neoplasia type 1 index cases. Genotype-negative patients with clinical multiple endocrine neoplasia type 1 had more pituitary macroadenomas, fewer prolactinomas, and more somatotroph adenomas. CONCLUSION: Genotype-negative patients with clinical multiple endocrine neoplasia type 1 have a different clinical course than genotype-positive multiple endocrine neoplasia type 1 index cases. This may support a separate classification and a tailored surveillance regimen. Of the genotype-negative patients with clinical multiple endocrine neoplasia type 1 who had parathyroidectomy, almost half had no evidence of multigland disease and may be potential candidates for a more targeted single-gland approach.


Assuntos
Hiperparatireoidismo Primário/epidemiologia , Neoplasia Endócrina Múltipla Tipo 1/terapia , Tumores Neuroendócrinos/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Hipofisárias/epidemiologia , Adulto , Fatores Etários , Idoso , Feminino , Seguimentos , Testes Genéticos/estatística & dados numéricos , Genótipo , Humanos , Hiperparatireoidismo Primário/genética , Hiperparatireoidismo Primário/terapia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/mortalidade , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Paratireoidectomia/estatística & dados numéricos , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/terapia , Proteínas Proto-Oncogênicas/genética , Estudos Retrospectivos , Fatores de Risco , Conduta Expectante
16.
ACS Appl Mater Interfaces ; 12(50): 56086-56094, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33259203

RESUMO

With the continuous improvement of the energy density of traction batteries for electric vehicles, the safety of batteries over their entire lifecycle has become the most critical issue in the development of electric vehicles. Abuse of electricity encountered in the application of batteries has a great impact on the safety of traction batteries. In this study, focused on the overdischarge phenomenon that is most likely to be encountered in the practical use of electric vehicles and grid storage, the impact of overdischarge on battery performance degradation is analyzed by neutron imaging technology and its safety hazards is systematically explored, combined with multimethods including electrochemical analysis and structural characterization. Results reveal the deterioration of the internal structure of traction batteries due to the overdischarge behavior and play a guiding role in the testing and evaluation of the safety of traction batteries.

17.
J Cell Mol Med ; 24(24): 14596-14607, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184989

RESUMO

Pancreatic cancer (PC) is a leading cause of cancer-related mortality globally. Though increasing evidence has demonstrated that circular RNAs (circRNAs) are linked to the development and progression of cancers, the biological functions of circRNAs in PC remain largely unexplored so far. Based on previous studies, Hsc_circ_0075829 (circ_0075829) was screened out and then further identified in PC clinical specimens and cell lines by real-time PCR. After the stability tests, a series of in vitro and in vivo functional experiments were performed to investigate the role of circ_0075829 in PC development. Furthermore, fluorescent in situ hybridization (FISH), bioinformatics tools, dual-luciferase assays and rescue experiments were conducted to clarify the regulatory mechanisms of circ_0075829 in SW1990 and BxPC-3 cells. Compared with paracancerous tissues, the expression of circ_0075829 was increased in PC tissues, which was positively correlated with the clinical features of PC. Knockdown of circ_0075829 significantly suppressed the proliferative, migratory and invasive rates of SW1990 and BxPC-3 cells both in vitro and in vivo. Bioinformatics analysis and dual-luciferase reporter gene assay indicated that circ_0075829 could bind to miR-1287-5p. Mechanism research and rescue experiments demonstrated that circ_0075829 could regulate the LAMTOR3/p-ERK signalling pathway via sponging miR-1287-5p in PC cell lines. Our data reveal that the circ_0075829 could facilitate the proliferation and metastasis of PC through circ_0075829/miR-1287-5p/LAMTOR3 axis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , RNA Circular , Transdução de Sinais , Adulto , Idoso , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Genes Reporter , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/diagnóstico , Interferência de RNA
18.
J Cell Mol Med ; 24(22): 13266-13277, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33090705

RESUMO

Circular RNAs (circRNAs) represent a newly discovered class of endogenous non-coding RNAs which are widely expressed and play important roles in disease progression. However, the function of circRNAs in oral squamous cell carcinoma (OSCC) still remains largely unknown. In this research, we found that circ_SEPT9 was highly expressed in OSCC cell lines and tumour tissues. Results showed that circ_SEPT9 promoted OSCC proliferation and tumour growth. And, circ_SEPT9 also enhanced the migration and invasion of OSCC cells. Mechanically, we found that circ_SEPT9 acted as a sponge for miR-1225 to rescue PKN2 expression in OSCC cells. Inhibition of circ_SEPT9/miR-1225/PKN2 pathway could effectively block the proliferation and metastasis of OSCC cells. Our study provides strong evidence that circ_SEPT9/miR-1225/PKN2 axis is a promising target for OSCC treatment.


Assuntos
Carcinoma de Células Escamosas/metabolismo , MicroRNAs/metabolismo , Neoplasias Bucais/metabolismo , Proteína Quinase C/metabolismo , RNA Circular/metabolismo , Septinas/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteínas do Citoesqueleto/metabolismo , Progressão da Doença , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço
19.
J Cell Mol Med ; 24(18): 10512-10524, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32691935

RESUMO

Dysregulation of long non-coding RNAs (lncRNAs) has been implicated in many cancer developments. Previous studies showed that lncRNA LINC00941 was aberrantly expressed in oral squamous cell carcinoma (OSCC). However, its role in OSCC development remains elusive. In this study, we demonstrated that in OSCC cells, EP300 activates LINC00941 transcription through up-regulating its promoter H3K27ac modification. Up-regulated LINC00941 in turn activates CAPRIN2 expression by looping to CAPRIN2 promoter. Functional assays suggest that both LINC00941 and CAPRIN2 play pivotal roles in promoting OSCC cell proliferation and colony formation. In vivo assay further confirmed the role of LINC00941 in promoting OSCC cell tumour formation. Lastly, we showed that the role of LINC00941 and CAPRIN2 in OSCC progression was mediated through activating the canonical WNT/ß-catenin signaling pathway. Thus, LINC00941/CAPRIN2/ WNT/ß-catenin signaling pathway provides new therapeutic targets for OSCC treatment.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Proteínas de Neoplasias/fisiologia , RNA Longo não Codificante/metabolismo , RNA Neoplásico/fisiologia , Proteínas de Ligação a RNA/fisiologia , Via de Sinalização Wnt/fisiologia , Animais , Sistemas CRISPR-Cas , Carcinoma de Células Escamosas/genética , Divisão Celular , Células Cultivadas , DNA de Neoplasias/genética , DNA de Neoplasias/ultraestrutura , Progressão da Doença , Proteína p300 Associada a E1A/fisiologia , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Código das Histonas , Queratinócitos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Bucais/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Transplante de Neoplasias , Regiões Promotoras Genéticas/genética , RNA Guia/administração & dosagem , RNA Guia/genética , RNA Longo não Codificante/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Proteínas de Ligação a RNA/biossíntese , Proteínas de Ligação a RNA/genética , Proteínas Recombinantes/metabolismo , Ensaio Tumoral de Célula-Tronco , Regulação para Cima , Via de Sinalização Wnt/genética
20.
PeerJ ; 8: e9065, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32391205

RESUMO

Hematopoiesis is a highly complex developmental process that produces various types of blood cells. This process is regulated by different genetic networks that control the proliferation, differentiation, and maturation of hematopoietic stem cells (HSCs). Although substantial progress has been made for understanding hematopoiesis, the detailed regulatory mechanisms for the fate determination of HSCs are still unraveled. In this study, we propose a novel approach to infer the detailed regulatory mechanisms. This work is designed to develop a mathematical framework that is able to realize nonlinear gene expression dynamics accurately. In particular, we intended to investigate the effect of possible protein heterodimers and/or synergistic effect in genetic regulation. This approach includes the Extended Forward Search Algorithm to infer network structure (top-down approach) and a non-linear mathematical model to infer dynamical property (bottom-up approach). Based on the published experimental data, we study two regulatory networks of 11 genes for regulating the erythrocyte differentiation pathway and the neutrophil differentiation pathway. The proposed algorithm is first applied to predict the network topologies among 11 genes and 55 non-linear terms which may be for heterodimers and/or synergistic effect. Then, the unknown model parameters are estimated by fitting simulations to the expression data of two different differentiation pathways. In addition, the edge deletion test is conducted to remove possible insignificant regulations from the inferred networks. Furthermore, the robustness property of the mathematical model is employed as an additional criterion to choose better network reconstruction results. Our simulation results successfully realized experimental data for two different differentiation pathways, which suggests that the proposed approach is an effective method to infer the topological structure and dynamic property of genetic regulations.

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