Circ_0007432 promotes non-small cell lung cancer progression and macrophage M2 polarization through SRSF1/KLF12 axis.

Circular RNAs (circRNAs) plays critical roles in non-small cell lung cancer (NSCLC) development. Herein, we illustrated the effects of circ_0007432 on malignant features of NSCLC. We found that circ_0007432 played a promoting role in NSCLC progression, lying in accelerating cell viability, migration and invasion of NSCLC cells, promoting M2 macrophage polarization, suppressing cell apoptosis of NSCLC cells, and enhancing tumor growth in vivo. Mechanistically, the interactions among circ_0007432, SRSF1, KLF12, and IL-8 were validated by RNA-binding protein immunoprecipitation (RIP), electrophoretic mobility shift assay (EMSA), RNA pull-down, dual luciferase reporter assay and chromatin immunoprecipitation (ChIP) assays. Circ_0007432 upregulated KLF12 by recruiting SRSF1. KLF12 facilitated IL-8 expression and release by binding to IL-8 promoter. Furthermore, the role of circ_0007432/SRSF1/KLF12/IL-8 axis in malignant phenotypes of tumor cells or macrophage polarization was investigated using rescue experiments. In conclusion, circ_0007432 bound with SRSF1 to stabilize KLF12 and then promote IL-8 release, thus promoting malignant behaviors of NSCLC cells and M2 macrophage polarization.

A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of clinical practice in China, and has accumulated a wealth of medical theories and treatment formulas, which has unique advantages in the prevention and treatment of malignant diseases. Traditional Chinese medicine may reduce the arrhythmic toxicity caused by chemotherapy without affecting the anti-cancer effect. This paper mainly discussed the types and pathogenesis of secondary chemotherapeutic drug-induced arrhythmia (CDIA), and summarized the studies on Chinese medicine compounds, Chinese medicine Combination Formula and Chinese medicine injection that may be beneficial in intervention with secondary CDIA including atrial fibrillation, ventricular arrhythmia and sinus bradycardia, in order to provide reference for clinical prevention and treatment of chemotherapy-induced arrhythmias.

The recent advance and prospect of natural source compounds for the treatment of heart failure.

Heart failure is a continuously developing syndrome of cardiac insufficiency caused by diseases, which becomes a major disease endangering human health as well as one of the main causes of death in patients with cardiovascular diseases. The occurrence of heart failure is related to hemodynamic abnormalities, neuroendocrine hormones, myocardial damage, myocardial remodeling etc, lead to the clinical manifestations including dyspnea, fatigue and fluid retention with complex pathophysiological mechanisms. Currently available drugs such as cardiac glycoside, diuretic, angiotensin-converting enzyme inhibitor, vasodilator and ß receptor blocker etc are widely used for the treatment of heart failure. In particular, natural products and related active ingredients have the characteristics of mild efficacy, low toxicity, multi-target comprehensive efficacy, and have obvious advantages in restoring cardiac function, reducing energy disorder and improving quality of life. In this review, we mainly focus on the recent advance including mechanisms and active ingredients of natural products for the treatment of heart failure, which will provide the inspiration for the development of more potent clinical drugs against heart failure.

SNX-2112 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Non-Small Cell Lung Cancer by Downregulating Epithelial-Mesenchymal Transition via the Wnt/ß-Catenin Signaling Pathway.

Lung cancer is the most frequent malignant tumor, and non-small cell lung cancer (NSCLC) is responsible for substantial mortality worldwide. The small molecule SNX-2112 was recently shown to critically effect the proliferation and apoptosis of tumor cells. Nevertheless, the precise mechanism by which SNX-2112 affects NSCLC remains poorly understood. Therefore, we investigated the function of SNX-2112 in NSCLC. We verified that SNX-2112 promoted apoptosis and suppressed the proliferation, invasion, and migration of A549 and H520 NSCLC cells in vitro. We further verified the potential mechanism of SNX-2112 in NSCLC. The changes in the protein levels demonstrated that SNX-2112 inhibited the epithelial-mesenchymal transition (EMT) (increased E-cadherin and decreased N-cadherin and vimentin) and the Wnt/ß-catenin signaling pathway (glycogen synthase kinase (GSK) 3ß and phosphorylated (p)-ß-catenin increased, ß-catenin and p-GSK3ß decreased) in NSCLC cells. These results were verified by rescue experiments using a Wnt/ß-catenin pathway agonist. We also established a tumor xenograft model and confirmed that SNX-2112 reduced tumor growth and proliferation and enhanced necrosis and apoptosis in a NSCLC model in vivo. In conclusion, the current study is the first to discover the mechanism of SNX-2112 in NSCLC. SNX-2112 induced apoptosis and also inhibited the proliferation, invasion, and migration of NSCLC cells by downregulating EMT via the Wnt/ß-catenin signaling pathway.

Author Correction: Complete genome sequence and transcriptomics analyses reveal pigment biosynthesis and regulatory mechanisms in an industrial strain, Monascus purpureus YY-1.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Targeted delivery of SNX-2112 by polysaccharide-modified graphene oxide nanocomposites for treatment of lung cancer.

Graphene oxide (GO) is a promising material for biomedical applications, particularly in drug delivery, due to its exceptional chemical and physical properties. In this work, an innovative GO-based carrier was developed by modifying GO with chitosan (CHI) to improve the biocompatibility, and followed by the conjugation of hyaluronic acid (HA), the target ligand for CD44, to realize the specific recognition of tumor cells and improve the efficiency of anti-tumor drug delivery. The resulting product GO-CHI-HA was loaded with an anti-cancer drug SNX-2112, which is the Hsp90 inhibitor. The total release amount and release rate of SNX-2112 were significantly higher in acidic condition than in physiological condition. GO-CHI-HA with a low concentration had little impact on the lysis of red blood cells (RBCs) and blood coagulation and showed low toxicity in A549 cells and NHBE cells. The GO-CHI-HA/SNX-2112 proved to be effective in inhibiting and killing A549 cells while having lower cytotoxicity against normal human bronchial epithelial cells (NHBE cells). Furthermore, in vivo toxicity of the materials towards vital organs in SD rats were also studied through histological examinations and blood property analyses, the results of which showed that although inflammatory response was developed in the short-term, GO-CHI-HA/SNX-2112 caused no severe long-term injury. Therefore, this drug delivery system showed great potential as an effective and safe drug delivery system with little adverse side effects for cancer therapy.

MicroRNA-28 promotes cell proliferation and invasion in gastric cancer via the PTEN/PI3K/AKT signalling pathway.

Gastric cancer is the fourth most common malignant disease and second leading cause of cancer­associated mortalities worldwide. Previous studies revealed aberrantly expressed microRNAs (miRNAs) in various types of human cancer; these miRNAs play important roles in tumourigenesis and tumour development. miRNAs present a considerable potential for novel therapeutic approaches for treating human cancer. Therefore, the investigation of novel miRNAs involved in gastric cancer progression provides an opportunity to improve the prognosis of patients with gastric cancer. miRNA­28 (miR­28) has been investigated with regards to its expression and biological functions in many types of human cancer. However, previous studies have not discussed the expression patterns, roles and associated molecular mechanisms of miR­28 in gastric cancer. In the present study, miR­28 expression was identified to be upregulated in gastric cancer tissues and cell lines. miR­28 inhibition functionally inhibited cell proliferation and invasion in gastric cancer in vitro. Using bioinformatics analysis, luciferase reporter assay, reverse transcription­quantitative polymerase chain reaction and western blot analysis, phosphatase and tensin homolog (PTEN) was mechanically identified as a direct target of miR­28 in gastric cancer. PTEN was downregulated in gastric cancer and negatively correlated with miR­28 levels. Inhibition of PTEN restored the biological effects of miR­28 downregulation on the proliferation and invasion of gastric cancer cells. Notably, the downregulation of miR­28 results in the regulation of the phosphatidylinositol 3­kinase/protein kinase B signaling pathway in gastric cancer. These results suggested that miR­28 may be targeted for the development of novel treatments for gastric cancer in the future.

Complete genome sequence and transcriptomics analyses reveal pigment biosynthesis and regulatory mechanisms in an industrial strain, Monascus purpureus YY-1.

Monascus has been used to produce natural colorants and food supplements for more than one thousand years, and approximately more than one billion people eat Monascus-fermented products during their daily life. In this study, using next-generation sequencing and optical mapping approaches, a 24.1-Mb complete genome of an industrial strain, Monascus purpureus YY-1, was obtained. This genome consists of eight chromosomes and 7,491 genes. Phylogenetic analysis at the genome level provides convincing evidence for the evolutionary position of M. purpureus. We provide the first comprehensive prediction of the biosynthetic pathway for Monascus pigment. Comparative genomic analyses show that the genome of M. purpureus is 13.6-40% smaller than those of closely related filamentous fungi and has undergone significant gene losses, most of which likely occurred during its specialized adaptation to starch-based foods. Comparative transcriptome analysis reveals that carbon starvation stress, resulting from the use of relatively low-quality carbon sources, contributes to the high yield of pigments by repressing central carbon metabolism and augmenting the acetyl-CoA pool. Our work provides important insights into the evolution of this economically important fungus and lays a foundation for future genetic manipulation and engineering of this strain.

[Therapeutic effect of interleukin-11 on thrombocytopenia in patients with hematologic malignancies after chemotherapy].

OBJECTIVE: To investigate and evaluate the clinical therapeutic effect of low-dose interleukin-11 treatment of thrombocytopenia in patients with malignant hematologic diseases after chemotherapy. METHODS: 70 patients with hematologic malignancies including acute leukemia, lymphoma and multiple myeloma were randomly divided into treatment group (35 cases) and control group (35 cases) and were treated with chemotherapy. Cases in the treatment group received subcutaneous injection of interleukin-11 (50 µg × kg(-1) × d(-1)) until platelet counting recovered ≥ 50 × 10(9)/L, while cases in the control group were not administrated with interleukin-11. RESULTS: The mean time of platelet recovery in the treatment group was 9.6 days, significantly shorter than that (14.0 days) in the control group (P < 0.05). The minimum platelet counting in the treatment group was significantly higher than that in the control group (16.2 × 10(9)/L vs. 11.6 × 10(9)/L, P < 0.05). The mean times of platelet infusion after chemotherapy in the treatment group and control group were 2.88 and 2.98, respectively (P > 0.05). CONCLUSION: Administration of interleukin-11 in thrombocytopenic patients with hematologic malignancies after chemotherapy may not only remarkably enhance platelet counts and shorten the recovery time of thrombocytopenia, but also has only mild side effects.