Silencing KLF16 inhibits oral squamous cell carcinoma cell proliferation by arresting the cell cycle and inducing apoptosis

Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.     

Future directions in managing aniridia-associated keratopathy

Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.     

Effects of age,gender and menstrual cycle on platelet function assessed by impedance aggregometry

Platelets are needed to prevent or arrest bleeding and aggregate at the site of injury upon vascular damage. Platelets express receptors for estrogens which might affect the function of the platelets and their hemostatic ability. The aim was to identify possible differences in platelet function related to age, gender, and phases of the menstrual cycle by use of impedance aggregometry with Multiplate. In the first part of the study, platelet function was assessed in 60 healthy individuals (30 men and 30 women) in each of three age groups (20–25, 40–45, and 60–65 years). In the second part of the study, the platelet function was analyzed on four occasions during the menstrual cycle in women without oral contraceptives (OCs) (n = 17) and compared to 19 women on OCs and 18 men of similar age (20–40 years). For the women on OCs, aggregation was analyzed once during the tablet-free week and once late during the period with OCs. The men were sampled once. Women of younger age (<45 years) had significantly higher agonist-induced aggregation response than both men and post-menopausal women (60–65 years). The agonist-induced aggregation response did not differ between phases of the menstrual cycle or OC use. The results suggest that estradiol and/or progesterone affect spontaneous aggregation since it was found to be lowest in the mid-luteal phase. Spontaneous aggregation was significantly lower in women on OCs than in both men and women without OCs. Our findings indicate that fertile age is associated with higher aggregation response capacity of the platelets, possibly to prevent excessive bleeding during menstruation, but this response capacity is not altered during the menstrual cycle or by use of OCs.     

Evaluation of circulating cell free DNA in plasma as a biomarker of different thyroid diseases

IntroductionMany studies have been done on proteomics, genomics, epigenetic, immunogenetics in many body fluids. Among these, circulating cell-free DNA (ccfDNA) entered the literature in 1948, but it has not been studied for many years due to technological deficiencies. Following recent advances, geno-metastasis has been mentioned and new research is needed in this area. ccfDNA is known to be an important biomolecule in this regard.ObjectiveThe presence of cell-free DNA in the circulatory system may offer a tremendous opportunity to provide novel biomarkers for thyroid diseases. This experimental study was conducted to determine the amount of ccfDNA in different thyroid diseases, then to evaluate whether the ccfDNA concentration varied between the disease groups and control group.MethodsIn total, we included 121 individuals in the present study. We collected blood samples and then determined the ccfDNA concentration in plasma of collected blood samples from three groups: thyroiditis (n = 33), benign (n = 37), and malignant (n = 30) and from a control group (n = 21).ResultsThe median values of the ccfDNA groups were found as 1610, 1665, 1685 and 576 ng/mL for the thyroiditis, benign, malign, and control groups, respectively. Findings showed that the ccfDNA of the three groups was significantly higher than the control (p < 0.0001). Each group was compared in terms of ccfDNA and the p-values of benign-thyroiditis, benign-malign, and thyroiditis-malign were 0.09, 0.65, and 0.29, respectively.ConclusionsThe clear differences between thyroid diseases and controls suggest that ccfDNA is worthy of attention as a biomarker for further evaluation of different thyroid diseases. Likewise, it might indicate a clear tendency that ccfDNA can also be used to distinguish different thyroid diseases.     

BCAN基因在肾透明细胞癌中的表达及临床意义

目的以基因表达数据集资料为研究对象,分析BCAN基因在肾透明细胞癌中的表达情况以及对患者预后的影响。方法在Oncomine数据库中挖掘BCAN在肾透明细胞癌(ccRCC)中的表达情况。从TCGA数据库中获取ccRCC患者临床资料和目的基因的表达信息并进行统计分析。利用GEO数据库中GSE73731数据集的ccRCC样本进行基因富集分析。利用String数据库分析与BCAN相关的蛋白。结果BCAN低表达组的ccRCC患者在病理分期及T分期方面低于高表达组(P<0.001;P=0.001);N分期及M分期差异无统计学意义(P>0.05)。BCAN低表达组患者的总生存期优于高表达组(P=0.033)。BCAN基因高表达组的样本主要富集在KRAS信号通路。结论BCAN可以通过多种途径来促进肿瘤细胞的侵袭能力,有望成为ccRCC不良预后的重要生物标志物之一。     

脑卒中患者恐惧疾病进展的研究现状

脑卒中患者在面对复杂的治疗期、漫长的康复期及难以预测的病情变化时容易产生对疾病或疾病进展的恐惧。恐惧疾病进展会损害脑卒中患者的身心健康和社会功能,最终影响患者的康复和预后。从恐惧疾病进展的定义、测量工具、国内外研究现状及影响因素几个方面进行综述,为临床护理人员深入了解脑卒中患者恐惧疾病进展现状、开展相关护理实践和临床研究提供依据。     

学龄期近视进展儿童调节功能的客观检查和分析

目的　对学龄期近视进展儿童进行调节功能的客观检查与分析，观察调节功能与近视进展之间的相关性。方法　选取2017年至2018年在首都医科大学附属北京同仁医院视光学门诊定期就诊的71名学龄期儿童为研究对象，根据受试者近年的屈光度进展速度，按≤0.50 D·a^-1、>0.50~1.00 D·a^-1、>1.00~1.50 D·a^-1、>1.50 D·a^-1分为4组，使用人眼调节分析仪对受试者进行调节功能的客观测量与分析，记录不同调节刺激视标下4组的客观调节反应值和客观调节微波动值，并作对比。结果　在所有调节视标上，各组随着调节刺激幅度增加，客观调节反应值也逐渐增加，4组在不同调节刺激视标下的客观调节反应值及平均的客观调节反应值差异均无统计学意义（均为P＞0.05）。≤0.50 D·a^-1、>0.50~1.00 D·a^-1、>1.00~1.50 D·a^-1、>1.50 D·a^-1近视进展速度组调节微波动值分别为（62.2±5.6）D、（62.5±5.3）D、（66.5±6.0）D和（58.0±6.5）D，4组间差异有统计学意义（F=6.424，P=0.001），在+0.50~-0.50 D、-2.00 D调节刺激视标下，4组的客观调节微波动值比较差异均有统计学意义（均为P＜0.05），在其余调节刺激视标下差异均无统计学意义（均为P＞0.05）。结论　对于学龄期儿童的近视进展速度，客观调节微波动值相对于客观调节反应值可能是一个更为敏感的相关指标。     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

Relationship between tRNA-derived fragments and human cancers

tRNA-derived fragments, a class of small noncoding RNAs (sncRNAs), have been identified in numerous studies in recent years. tRNA-derived fragments are classified into two main groups, including tRNA halves (tiRNAs) and tRNA-derived small RNA fragments (tRFs), according to different cleavage positions of the precursor or mature tRNAs. Instead of random tRNA degradation debris, a growing body of evidence has shown that tRNA-derived fragments are precise products of specific tRNA modifications and play important roles in biological activities, such as regulating protein translation, affecting gene expression, and altering immune signaling. Recently, the relations between tRNA-derived fragments and the occurrence of human diseases, especially cancers, have generated wide interest. It has been demonstrated that tRNA-derived fragments are involved in cancer cell proliferation, metastasis, progression and survival. In this review, we will describe the biogenesis of tRNA-derived fragments, the distinct expression and function of tRNA-derived fragments in the development of cancers, and their emerging roles as diagnostic and prognostic biomarkers and precise targets of future treatments.