Search

To investigate the regulatory effect and mechanism of circular RNA PVT1 (circPVT1) in proliferation and chemoresistance of osteosarcoma (OS) cells.The expression of circPVT1 in human OS and adjacent normal tissues was detected. The correlation between circPVT1 expression and clinical features of OS was analyzed. The expressions of circPVT1 and miR-24-3p in OS cells resistant to cisplatin, doxorubicin or methotrexate and parental OS cells were detected after cell transfection. CCK-8 and colony formation assay assessed the viability and proliferative ability of OS cells. qRT-PCR and Western blotting measured the expression of KLF8. Dual-luciferase reporter and RNA pull-down assays verified the targeting relationships of circPVT1/miR-24-3p and miR-24-3p/KLF8.CircPVT1 was over-expressed in OS tissues and cells, and correlated with clinical features of OS. Over-expressed circPVT1 reduced the survival of OS patients. CircPVT1 was up-regulated in chemoresistant OS cells compared to their parental cells. CircPVT1 inhibition suppressed the proliferation and chemoresistance of OS cells. MiR-24-3p was under-expressed in OS cells and further down-regulated in chemoresistant cells. CircPVT1 could bind and down-regulate miR-24-3p. MiR-24-3p overexpression inhibited the proliferation and chemoresistance of OS cells. KLF8 was over-expressed in OS cells and further up-regulated in chemoresistant cells. MiR-24-3p negatively regulated the expression of KLF8.CircPVT1 mediates proliferation and chemoresistance of OS cells via the miR-24-3p/KLF8 axis. The findings may provide guidance for clinical treatment of OS.

Sarcomas are a broad family of cancers that arise from cells of mesenchymal origin in virtually every tissue of the body. Some transcription factors (TFs) have been reported to be involved in the pathogenesis and metastasis of sarcomas. The expression of certain long noncoding RNAs (lncRNAs) has been correlated with the degree of cancer prognosis. There is an urgent need to effectively integrate TFs and lncRNA/microRNA/mRNA regulatory axis and further identify more key regulators that play crucial roles in sarcomas. We performed a network-based computational analysis to investigate the lncRNA-TF cross talks via integrating lncRNA-TF ceRNA interactions and TF-TF protein-protein interactions. Multiple topology analyses were performed to the sarcomas-related global lncRNA-TF network. Several lncRNAs or TFs with central topology structures were identified as key regulators and used to locate a hub-associated lncRNA-TF subnetwork. Three functional modules were identified from the sarcomas-related global lncRNA-TF network, which have shown significant pathway enrichment and prognosis capability. The lncRNAs and TFs of these modules were shown to participate in sarcoma-related biological phenomena through involving in mitogen-activated protein kinases (MAPK), Jak-STAT, and transforming growth factor (TGF-beta) signaling pathways. More importantly, a subset of core lncRNA-TF cross talks that might form positive feedback loops to control biological processes of sarcomas was identified. These core lncRNA-TF positive feedback loops showed more TF binding affinity than other lncRNAs. All the results can help us uncover the molecular mechanism of sarcomas and provide a novel way for diagnosis biomarker and therapeutic target identification.

Cancer immunotherapy has achieved positive clinical responses in the treatment of various cancers, including gastric cancer (GC). In this study, we characterized the heterogeneity of T cells isolated from GC patients at the single-cell level using single-cell RNA sequencing. We identified different immune cell subtypes and their heterogeneous transcription factors and depicted their developmental trajectories. In particular, we focused on exhausted CD8+ cells and Tregs and discovered that, as compared to control, the IRF8 transcription factor was downregulated in CD8+ tumour-infiltrating lymphocytes (TILs) from GC tissues, and that GC patients with lower IRF8 levels in blood CD8+ T cells tended to be a at a more advanced disease stage. These findings provide a theoretical basis for targeted immune therapy in GC.

PiRNAs are a small class of non-coding small RNAs newly discovered in recent years. Millions of piRNAs have been discovered to date, and more than 20,000 piRNA genes have been found in the human genome. Due to the relatively small number of studies related to piRNA, our understanding of piRNAs is very limited. Currently, the clear biological function of piRNAs is transposon mobilization inhibition by promoting transcript degradation and regulating chromatin formation. In addition, piRNAs can form piRNA-PIWI protein complexes with some members of the PIWI branch of the Argonaute protein. Based on these biological functions, piRNAs and PIWI proteins are important in maintaining the genomic integrity of germline cells. Because of this, the popularity of piRNAs research has been focused on its role in germline cells for a long time after the discovery of piRNAs. As the field of research expands, there is growing evidence that piRNAs and PIWI proteins are abnormally expressed in various types of cancers, which may be potential cancer biomarkers and cancer therapeutic targets. In this review, we will focus on the relationship between piRNAs and PIWI proteins and cancers based on previous research, as well as their significance in cancer detection, grading and treatment.

Objective This study investigated the effects of leptin on intestinal flora and inflammation in mice with high-fat diet (HFD)-induced obesity. Methods Mice were fed an HFD for 8 weeks; some were concurrently administered oral leptin for 4 weeks. Pathological changes in adipose tissue were detected using hematoxylin–eosin staining; endotoxin content in adipose tissue was measured by enzyme-linked immunosorbent assay. Intestinal flora were characterized by 16S bacterial rDNA sequencing. Levels of Toll-like receptor 4 (TLR4), nuclear factor-κB inhibitor α (IκB-α), and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected by western blotting. Results Mice in the HFD group exhibited weight gain, elevated endotoxin content, and adipocyte hypertrophy, compared with the non-obese control group. Moreover, abundance of bacteria in the Bacteroides genus and community diversity were both reduced in the HFD group; reductions also were observed at corresponding phylum, class, and order levels. Levels of TLR4, IκB-α, and p-JNK were also elevated in the HFD group. Compared with the model group, leptin administration reduced the weight gain and endotoxin content, while increasing Bacteroides abundance and community diversity; it also reduced the levels of TLR4, IκB-α, and p-JNK. Conclusion Leptin administration improved intestinal flora dysfunction and inflammation in mice with HFD-induced obesity.

Rationale: A 27-year-old woman with a history of systemic lupus erythaematosus (SLE) developed hemophagocytic syndrome (HPS) secondary due to an unrecognized infection that led to severe SLE with a prolonged recovery. Patient concerns: The patient showed a high spiking fever and myalgia. Laboratory data revealed pancytopenia and immunological abnormalities. Pulse methylprednisone plus intravenous immunoglobulin (IVIG) failed to improve the clinical symptoms and laboratory data. Diagnoses: As activated macrophages with hemophagocytosis were confirmed in bone marrow histology, the patient was diagnosed as having reactive HPS. Interventions and outcomes: Her reactive HPS was successfully treated with intravenous antibiotics and was followed by oral prednisolone and hydroxychloroquine maintenance therapy. Lessons: In severe SLE, patients with persistent high fever, cytopenia, and elevated levels of serum ferritin and liver enzymes should be strongly suspected of reactive HPS, and aggressive examination, such as bone marrow biopsy, needs to be considered for early diagnosis and proper treatment.

Objective We explored the association between single nucleotide polymorphisms (SNPs) rs207454 and rs494852 located in xanthine dehydrogenase (XDH) and gastric cancer (GC) survival. Methods A total of 940 patients with gastric cancer were enrolled and genotyped using TaqMan allelic discrimination method. The Kaplan–Meier test and log-rank examine were used to assess the effect of genetic variation. Results Patients carrying rs207454 CC genotype had a longer survival time than those with the AA genotype (P = 0.042). The similar association was detected in the recessive model (P = 0.017). We conducted expression quantitative trait loci (eQTL) analysis and found that gastric cancer patients carrying rs207454 CC genotype had significant lower XDH levels than those with AA/AC genotype, suggesting that rs207454 polymorphism effected the expression of XDH. Additionally, the Kaplan-Meier curves showed that gastric cancer patients with high expression of XDH had remarkably poor survival outcome than those with low expression (hazard ratio [HR] = 1.53, 95% confidence interval [CI] = 1.29–1.82). Conclusions Genetic variants in XDH were associated with the survival of gastric cancer and may act as prognostic markers for individual suffered from gastric cancer.

The aim of this study was to determine whether in vitro fertilization (IVF) outcomes are associated with inherited thrombophilias.Several databases including PubMed, Embase, and Cochrane Library were retrieved up to 12 January 2016. The quality of the included studies was assessed by two authors. The associations of the following mutations in inherited thrombophilias and IVF outcomes were explored: factor V Leiden (FVL), prothrombin gene G20210A mutation (PGM), 5,10-methylentetrahydrofolate reductase (MTHFR) C677T, MTHFR (A1298C) and activated protein C resistance (APCR). The main outcome measures included CPR and implantation rate (IR). The relative risk (RR) and its 95 % confidence interval (CI) were calculated for effect index. Heterogeneity test was evaluated by Chi-square based on Q statistic and I (2) statistics.A total of seven articles published between 2007 and 2015 with the ages of subjects between 30.9 and 36.2 were included. For subgroups analysis of CPR or IR, there were no significant differences in MTHFR (C377T), MTHFR (A1298C), FVL, PGM, and FVL/PGM mutation were found between the mutation group and control group (P 0. 05).IVF outcomes are not associated with FVL, PGM, MTHFR (C677T), MTHFR (A1298C), and APCR mutation in inherited thrombophilias.

Background In the past decades, a good deal of studies has provided the possibility of the circulating microRNAs (miRNAs) as noninvasive biomarkers for cancer diagnosis. The aim of our study was to detect the levels of circulating miRNAs in tissues and plasmas of gastric cancer (GC) patients and evaluate their diagnostic value. Methods Tissue samples were collected from 85 GC patients. Plasma samples were collected from 285 GC patients and 285 matched controls. Differentially expressed miRNAs were filtered with by Agilent Human miRNA Microarray and TaqMan low density array (TLDA) with pooled samples, followed by the quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation. Receiver operating characteristic (ROC) curves were structured to evaluate the diagnostic accuracy of the miRNAs. The plasma level of miR-26a in GC patients of different clinical stages was compared. Results Four miRNAs (miR-26a, miR-142-3p, miR-148a, and miR-195) revealed coincidentally decreased levels in tissue and plasma of the GC patients compared with controls, and ROC curves were constructed to demonstrate that miR-26a had a highest area under the ROC curve (AUC) of 0.882. Furthermore, miR-26a was stably detected in the plasma of GC patients with different clinical characteristics. Conclusion Plasma miR-26a may provide a novel and stable marker of gastric cancer.

Dermatophagoides farinae, or the American house dust mite, is a common cause of allergy and asthma. Current tests for sensitization to D. farinae include an indirect enzyme-linked immunosorbent assay (ELISA) method for specific IgE detection, which, while clinically useful, is time-consuming and has low sensitivity since it uses crude mite extracts. We developed two new ELISA methods to detect the group 2 allergen from D. farinae (Der f 2) and the Der f 2-specific IgE in sera of patients with asthma. Using recombinant Der f 2 protein for the analysis of Der f 2-specific IgE, we tested both indirect ELISA and avidin biotin complex ELISA (ABC-ELISA) methods in 46 patients who were also tested by Pharmacia UniCap. Both of these approaches are more specific than traditional methods using crude mite extracts. These new tests could aid in the laboratory diagnosis of asthma due to sensitization to D. farinae.