RESUMO
Krüppel-like factors (KLFs) are transcription factors that control the expression of downstream genes. The role of KLFs has been reported in cancers. KLF16 promotes the proliferation of gastric cancer cells by upregulating p21, while suppresses the tumorigenesis of glioma through targeting TFAM. The function of KLF16 is controversial in cancer development. In this study, we aimed to investigate the role of KLF16 in retinoblastoma (RB). KLF16 was highly expressed in RB tissues and cells. Overexpression of KLF16 promoted the proliferation, growth and migration of RB cells. By contrast, KLF16 interference showed opposite effects. Cell cycle arrest and apoptosis were induced or repressed by KLF16 knockdown or overexpression, respectively. Mechanistically, BCL2 like 15 (BCL2L15), an apoptosis gene, was negatively regulated by KLF16. Luciferase reporter and ChIP assay showed that KLF16 transcriptionally repressed the expression of BCL2L15 by binding to its promoter. BCL2L15 was lowly expressed in RB tissues. Additionally, overexpression of BCL2L15 inhibited the proliferation and increased the apoptosis in RB cells. Our study identifies that KLF16 contributes to RB cell proliferation and migration by negatively regulating BCL2L15.
Assuntos
Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição Kruppel-Like/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Neoplasias da Retina/genética , Epitélio Pigmentado da Retina/metabolismo , Retinoblastoma/genética , Apoptose/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Genes Reporter , Humanos , Fatores de Transcrição Kruppel-Like/antagonistas & inibidores , Fatores de Transcrição Kruppel-Like/metabolismo , Luciferases/genética , Luciferases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Neoplasias da Retina/metabolismo , Neoplasias da Retina/patologia , Epitélio Pigmentado da Retina/patologia , Retinoblastoma/metabolismo , Retinoblastoma/patologia , Transdução de Sinais , Transcrição GênicaRESUMO
AIM: To analyze the differences in immune indicators and prognosis between IgG4-positive and negative lacrimal gland benign lymphoepithelial lesion (LGBLEL). METHODS: This was a single-center retrospective clinical study including 105 cases of IgG4-positive LGBLEL and 41 cases of IgG4-negative LGBLEL. Basic information, related indicators of peripheral venous blood samples using immunoscattering turbidimetry, treatment (partial surgical excision and glucocorticoid therapy) and prognosis (recurrence and death) were collected. Survival curves for recurrence were created using the Kaplan-Meier analysis. Univariate analysis and multivariate regression analysis were used to analyze prognostic factors. RESULTS: The mean age was 50.10±14.23y and 44.76±11.43y (P=0.033) in IgG4-positive and negative group respectively. The serum C3 and C4 was lower in IgG4-positive group (P=0.005, P=0.002), while the serum IgG and IgG2 was higher in IgG4-positive group (P=0.000 and P=0.008). Twenty-one cases had recurrence in IgG4-positive group and 3 cases recurrence in IgG4-negative group. The 5-year recurrence-free cumulative percentages of IgG4-positive group was 81.85%, and 83.46% in the IgG-negative group (P=0.216). The history of preoperative glucocorticoid therapy, serum C4, IgG1 and IgG2 were the factors affecting recurrence in IgG4-positive group, while serum C4, and IgG1 were the factors affecting recurrence of LGBLEL. CONCLUSION: Serum C4 and IgG1 are the factors affecting recurrence of LGBLEL, while the IgG4 does not affect recurrence of LGBLEL.
RESUMO
AIM: To evaluate the survival outcomes of patients with lacrimal gland adenoid cystic carcinoma who underwent eye-sparing surgery combined with 125I seed implantation radiotherapy or local external γ-ray radiotherapy. METHODS: In this retrospective comparative case series, the clinical records of 27 primary and 8 recurrent patients were reviewed. Univariate and multivariate analyses were used to identify risk factors associated with distant metastasis (DM), and the overall survival (OS) after the initial surgery was analyzed. RESULTS: The median follow-up after radiotherapy was 36mo (range 6-120mo). At the last follow-up after radiotherapy, 26 (74.3%) patients had no evidence of disease, 7 (20%) patients had DM, 2 (5.9%) patients died of DM, and 1 patient with DM was lost to follow-up. Univariate analyses showed that duration of symptoms, bone destruction, T stage classification, and wide excision surgery were risk factors influencing DM (P<0.05). The 5-year and 10-year OS rates after the initial surgery were 95.8% and 79.9%, respectively. The 5-year DM-free survival and disease-free survival rates after radiotherapy were 66.4% and 52.7%, respectively. CONCLUSION: 125I seed radiotherapy and local external γ-ray radiotherapy may have similar therapeutic effects in preventing DM. Patients with T1/T2 stage disease have a better prognosis than those with T3/T4 stage disease.
RESUMO
BACKGROUND: Environmental variation related to ecological habitat is the main driver of plant adaptive divergence. Longitude plays an important role in the formation of plant population structure, indicating that environmental differentiation can significantly shape population structure. METHODS: Genetic diversity and population genetic structure were estimated using 105 expressed sequence tag-derived simple sequence repeat (EST-SSR) loci. A total of 249 C. dactylon (L.) Pers. (common bermudagrass) individuals were sampled from 13 geographic sites along the longitude (105°57'34â³-119°27'06â³E). RESULTS: There was no obvious linear trend of intra-population genetic diversity along longitude and the intra-population genetic diversity was not related to climate in this study. Low gene flow (Nm = 0.7701) meant a rich genetic differentiation among populations of C. dactylon along longitude gradients. Significantly positive Mantel correlation (r = 0.438, P = 0.001) was found between genetic distance and geographical interval while no significant partial Mantel correlation after controlling the effect of mean annual precipitation, which indicated geographic distance correlated with mean annual precipitation affect genetic distance. The genetic diversity of C. dactylon with higher ploidy level was higher than that with lower ploidy level and groups of individuals with higher ploidy level were separated further away by genetic distance from the lower ploidy levels. Understanding the different genetic bases of local adaptation comparatively between latitude and longitude is one of the core findings in the adaptive evolution of plants.
RESUMO
BACKGROUND: The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19. METHODS: Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size. RESULTS: Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (ORâ=â0.34, 95% CI: 0.20-0.56, moderate quality) and COR (ORâ=â0.84, 95% CI: 0.75-0.96, low quality) with improved cure rate (ORâ=â2.16, 95% CI: 1.60-2.91, low quality for TCM; ORâ=â1.17, 95% CI: 1.05-1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (ORâ=â3.20, 95% CI: 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (ORâ=â0.52, 95% CI: 0.38-0.70, very low quality) but CQ_HD (ORâ=â2.51, 95% CI: 1.20-5.24) and interferons (IFN) (ORâ=â2.69, 95% CI: 1.02-7.08) vs. SOC with very low quality were associated with an increased risk. CONCLUSIONS: COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.
Assuntos
COVID-19 , Humanos , Medicina Tradicional Chinesa , Metanálise em Rede , Pandemias , SARS-CoV-2RESUMO
Cynodon dactylon (L.) Pers. (common Bermuda grass) has a limited capacity to grow at low temperatures, which limits its geographical range. Exploring its evolutionary relationship across different environmental gradients is necessary to understand the effects of temperature change on the genetics of common Bermuda grass. In this study, high-throughput transcriptome sequencing was performed on 137 samples of C. dactylon from 16 latitudinal gradients to explore the differential molecular markers and analyze genetic diversity and structure along latitudinal gradients at different temperatures. We primarily sampled more high-quality single nucleotide polymorphisms (SNPs) from populations at lower and middle latitudes. Greater intraspecific genetic variation at each level of temperature treatment could be due to factors such as wind pollination and asexual breeding. Populations of C. dactylon at high latitudes differed from populations at middle and low latitudes, which was supported by a principal component analysis (PCA) and genetic structure analysis, performed at different temperatures. We observed more genetic variation for low-latitude populations at 5 °C, according to an analysis of three phylogenetic trees at different temperature levels, suggesting that low temperatures affected samples with low cold resistance. Based on the results of phylogenetic analysis, we found that samples from high latitudes evolved earlier than most samples at low latitudes. The results provide a comprehensive understanding of the evolutionary phenomenon of landscape genetics, laying the groundwork for future structural and comparative genomic studies of C. dactylon.
RESUMO
Purpose: To examine the early glial reactivity and neuron damage in response to short-term cerebrospinal fluid pressure (CSFp) reduction, as compared with intraocular pressure (IOP) elevation. Methods: The experiment included 54 male Sprague-Dawley rats with elevated translaminar cribrosa pressure difference (TLPD), defined as IOP minus CSFp. These rats underwent either continuous CSF drainage for 6 hours (n = 18), or unilateral IOP elevation to 40 mm Hg for 6 hours (n = 18). For control, 18 normal rats were anesthetized for 6 hours. Orthograde axonal transport was examined by intravitreal injection of 3% rhodamine-ß-isothiocyanate. We also used transmission electron microscopy to display the ultrastructural features of retinal ganglion cell axons in the optic nerve head. Early glial reactivity in the retina, lateral geniculate nucleus (LGN), and superior colliculus (SC) was detected by immunostaining and Western blot for the glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). We also observed the glial reactivity in the inferior colliculus and hippocampus to rule out possible influences of CSF dynamics and composition. Results: Anterograde staining with 3% rhodamine-ß-isothiocyanate revealed decreased fluorescence intensity of the SC and LGN projected from both lower CSFp and higher IOP eyes. Transmission electron microscopy showed loss of axons from the optic nerve head in the high-IOP group, but not in the low-CSFp group. Compared with the anesthesia control group, GFAP expression was significantly increased in the retina, LGN, and SC, whereas GS expression was only increased in the retina following CSFp reduction. However, their expressions were not significantly elevated in the inferior colliculus and hippocampus. In the high-IOP group, expressions of GFAP and GS were significantly increased in the retina, LGN, and SC. Conclusions: Visual system neurons may be much more sensitive than other nervous tissues. Following short-term CSFp reduction, early glial reactivity may precede axonal loss. Changes of translaminar cribrosa pressure difference in both experimental low-CSFp and high-IOP groups induce selective early glial reactivity. The neuron damage from abnormally low CSFp may be pathogenetically similar to high IOP.
Assuntos
Axônios/patologia , Pressão do Líquido Cefalorraquidiano/fisiologia , Neuroglia/patologia , Disco Óptico/patologia , Doenças do Nervo Óptico/fisiopatologia , Células Ganglionares da Retina/patologia , Vias Visuais/patologia , Animais , Axônios/ultraestrutura , Western Blotting , Técnica Indireta de Fluorescência para Anticorpo , Corpos Geniculados/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Glutamato-Amônia Ligase/metabolismo , Pressão Intraocular/fisiologia , Masculino , Microscopia Eletrônica de Transmissão , Disco Óptico/ultraestrutura , Ratos , Ratos Sprague-Dawley , Células Ganglionares da Retina/ultraestrutura , Colículos Superiores/metabolismoRESUMO
Retinal degenerative diseases pose a serious threat to eye health, but there is currently no effective treatment available. Recent years have witnessed rapid development of several cutting-edge technologies, such as gene therapy, stem cell therapy, and tissue engineering. Due to the special features of ocular structure, some of these technologies have been translated into ophthalmological clinic practice with fruitful achievements, setting a good example for other fields. This paper reviews the development of the gene and stem cell therapies in ophthalmology.
RESUMO
AIM: To report the abnormal type of the orbital liposarcoma-dedifferentiated subtype in a patient. METHODS: A case report. RESULTS: A 23 years old Chinese woman with a recurrence of right-sided proptosis was evaluated. Ocular examination revealed proptosis of the right eye with chemosis, hyperemia and limitation of eye movements. Magnetic resonance imaging scanning showed an irregular shaped tumor in the right orbit. The tumor resection was done with a clinical diagnosis of malignant tumor. Histopathological findings revealed the diagnosis of dedifferentiated liposarcoma. CONCLUSION: The rare occurrence of this tumour should be kept in mind while dealing with orbital tumours.