Glioblastoma is the most common and lethal primary intracranial tumor. As the key regulator of tumor cell volume, sodium‐potassium‐chloride cotransporter 1 (NKCC1) expression increases along with the malignancy of the glioma, and NKCC1 has been implicated in glioblastoma invasion. However, little is known about the role of NKCC1 in the epithelial‐mesenchymal transition‐like process in gliomas. We noticed that aberrantly elevated expression of NKCC1 leads to changes in the shape, polarity, and adhesion of cells in glioma. Here, we investigated whether NKCC1 promotes an epithelial–mesenchymal transition (EMT)‐like process in gliomas via the RhoA and Rac1 signaling pathways. Pharmacological inhibition and knockdown of NKCC1 both decrease the expressions of mesenchymal markers, such as N‐cadherin, vimentin, and snail, whereas these treatments increase the expression of the epithelial marker E‐cadherin. These findings indicate that NKCC1 promotes an EMT‐like process in gliomas. The underlying mechanism is the facilitation of the binding of Rac1 and RhoA to GTP by NKCC1, which results in a significant enhancement of the EMT‐like process. Specific inhibition or knockdown of NKCC1 both attenuate activated Rac1 and RhoA, and the pharmacological inhibitions of Rac1 and RhoA both impair the invasion and migration abilities of gliomas. Furthermore, we illustrated that NKCC1 knockdown abolished the dissemination and spread of glioma cells in a nude mouse intracranial model. These findings suggest that elevated NKCC1 activity acts in the regulation of an EMT‐like process in gliomas, and thus provides a novel therapeutic strategy for targeting the invasiveness of gliomas, which might help to inhibit the spread of malignant intracranial tumors.

Numerous studies have shown that calmodulin (CaM) is a major regulator of calcium-dependent signaling, which regulates cell proliferation, programmed cell death, and autophagy in cancer. However, limited information is available on mechanisms underlying the effect of CaM on the invasive property of glioblastoma multiforme (GBM) cells, especially with respect to invadopodia formation. In this study, we find that CaM serves as a prognostic factor for GBM, and it is strongly associated with the invasive nature of this tumor. Results of preliminary experiments indicated that CaM concentration was significantly correlated with the invasive capacity of and invadopodia formation by different GBM cell lines. CaM inhibition via a small hairpin RNA or a pharmacological inhibitor significantly disrupted invadopodia formation and MMP activity and downregulated vimentin expression. Moreover, CaM knockdown exerted a strong anti-invasive effect on GBM in vivo. Interestingly, epidermal growth factor treatment promoted CaM redistribution from the nucleus to the cytoplasm, eventually activating invadopodia-associated proteins by binding to them via their cytosolic-binding sites. Moreover, CaM inhibition suppressed the activation of invadopodia-associated proteins. Thus, our findings provide a novel therapeutic strategy to impede GBM invasion by inhibiting invadopodia formation, and shed light on the spatial organization of CaM signals during GBM invasion.

Wistar rats were randomly divided into groups of varying iodide intake: normal iodide; 10 times high iodide; and 100 times high iodide on Days 7, 14, and 28. Insignificant changes were observed in thyroid hormone levels (p > 0.05). Urinary iodine concentration and iodine content in the thyroid glands increased after high consumption of iodide from NI to 100 HI (p < 0.05). The urinary iodine concentration of the 100 HI group on Days 7, 14, and 28 was 60–80 times that of the NI group. The mitochondrial superoxide production and expressions of Nrf2, Srx, and Prx 3 all significantly increased, while Keap 1 significantly decreased in the 100 HI group when compared to the NI or 10 HI group on Days 7, 14, and 28 (p < 0.05). Immunofluorescence staining results showed that Nrf2 was localized in the cytoplasm in NI group. Although Nrf2 was detected in both cytoplasm and nucleus in 10 HI and 100 HI groups, a stronger positive staining was found in the nucleus. We conclude that the activation of the Nrf2-Keap 1 antioxidative defense mechanism may play a crucial role in protecting thyroid function from short-term iodide excess in rats.

Glioblastoma multiforme (GBM) is one of the most lethal types of tumour, despite severe treatment methods. The Cancer Genome Atlas has categorised GBMs into proneural, neural, classical and mesenchymal subtypes; the mesenchymal subgroup has the worst prognosis. CXCR4 has been reported as selectively overexpressed in the mesenchymal subtype and positively associated with MES markers. However, to the best of our knowledge the underlying mechanisms regarding how CXCR4 may regulate mesenchymal GBM are still unknown. The present study aimed to investigate the critical pathways mediated by CXCR4 in mesenchymal GBM using bioinformatic analyses. The results suggested that CXCR4 is a predictor of poor prognosis and may serve as a biomarker of the mesenchymal subtype in patients with GBM. In addition, CXCR4 mediated the mitogen-activated protein kinase signaling pathway, which was identified specifically in patients with mesenchymal GBM. CXCR4 associated genes or pathways may be a ‘basket trial’ option for the management of melanoma, prostate cancer and mesenchymal GBM.

Objectives:To determine the validity of uric acid as a potential prognostic marker for long-term outcomes of patients with acute myocardial infarction (AMI) and those with AMI undergoing percutaneous coronary intervention (PCI).Methods:Systematic review and meta-analysis were performed. We retrieved data from retrospective and prospective cohort studies that investigated whether serum uric acid (SUA) level affects the prognosis of patients with AMI.Results:Thirteen studies involving 9371 patients were included. High serum uric acid (HSUA) level increased mid/long-term mortality (risk ratio (RR)=2.32, 95% confidence intervals (CI): 2.00–2.70) and had higher short-term mortality (RR=3.09, 95% CI: 2.58–3.71), higher mid/long-term major adverse cardiovascular events (MACE) risk (RR=1.70, 95% CI: 1.54–1.88), and higher short-term MACE risk (RR=2.47, 95% CI: 2.08–2.92) for patients with AMI. In the PCI subgroup, the HSUA level also increased mid/long-term mortality (RR=2.33, 95% CI: 1.89 to 2.87) and had higher mid/long-term MACE risk (RR=1.64, 95% CI: 1.48–1.82), and higher short-term MACE risk (RR 2.43, 95% CI: 2.02–2.93) for patients who were treated with PCI after AMI. Particularly in the PCI subgroup, a higher short-term mortality (RR=6.70, 95% CI: 3.14–14.31) was presented in the group with lower HSUA cut-off level, and the mortality was higher than the group with higher HSUA cut-off level (RR=2.69, 95% CI: 2.09–3.46).Conclusion:The HSUA level significantly increased the mortality and MACE risk of patients with AMI. Mild elevation of SUA levels (normal range) have started to have a significant impact on the short-term mortality of patients who underwent PCI, and has not received the attention of previous studies. However, this condition should be further investigated.

Object: To explore the critical role of growth differentiation factor 11 (GDF11) in the pathobiology of aplastic anemia (AA). Methods: We have examined the serum GDF11 levels for 79 AA patients and 30 healthy controls. A total of 79 AA patients, which included 29 new diagnosed (untreated) cases, 14 cases with no response, 21 partial remission (PR) cases and 15 complete remission (CR) cases after immunosuppressive therapy (IST). GDF11 serum levels were assessed by an enzymelinked immunosorbent assay. GDF11 mRNA expression in peripheral blood mononuclear (PBMNC) was detected through real time polymerase chain reaction. The correlation between GDF11 expression and erythropoietic function was evaluated. Results: The serum GDF11 levels in untreated AA patients were higher than that of the control group. The serum GDF11 levels of PR patients or CR patients after IST was decreased, compared with untreated patients, but did not recover back to the normal levels. GDF11 levels had a negative correlation with hemoglobin (Hb) levels and reticulocyte counts in AA patients. GDF11 levels did not correlate with age, sex and severity of in AA patients. Conclusion: Serum GDF11 levels were increased and negatively correlated with Hb levels and reticulocyte counts in AA patients. This suggests an impaired GDF11 response contributing to anemia in AA patients.

Glioblastoma multiforme (GBM) is a fatal cancer with varying life expectancy, even for patients undergoing the same standard therapy. Identification of differentially expressed genes in GBM patients with different survival rates may benefit the development of effective therapeutic strategies. In the present study, key pathways and genes correlated with survival in GBM patients were screened with bioinformatic analysis. Included in the study were 136 eligible patients who had undertaken surgical resection of GBM followed by temozolomide (TMZ) chemoradiation and long-term therapy with TMZ. A total of 383 differentially expressed genes (DEGs) related to GBM survival were identified. Gene Ontology and pathway enrichment analysis as well as hub gene screening and module analysis were performed. As expected, angiogenesis and migration of GBM cells were closely correlated with a poor prognosis. Importantly, the results also indicated that cell dormancy was an essential contributor to the reduced survival of GBM patients. Given the lack of specific targeted genes and pathways known to be involved in tumour cell dormancy, we proposed enriched candidate genes related to the negative regulation of cell proliferation, signalling pathways regulating pluripotency of stem cells and neuroactive ligand-receptor interaction, and 3 hub genes (FTH1, GRM1 and DDIT3). Maintaining persistent cell dormancy or preventing tumour cells from entering dormancy during chemoradiation should be a promising therapeutic strategy.

BackgroundIncreased oxidative stress has been suggested as one of the underlying mechanisms in iodide excess-induced thyroid disease. Metallothioneins (MTs) are regarded as scavengers of reactive oxygen species (ROS) in oxidative stress. Our aim is to investigate the effects of propylthiouracil (PTU), a thyroid peroxidase inhibitor, perchlorate (KClO4), a competitive inhibitor of iodide transport, and thyroid stimulating hormone (TSH) on mitochondrial superoxide production instigated by high concentrations of iodide in the thyroids of MT-I/II knockout (MT-I/II KO) mice.MethodsEight-week-old 129S7/SvEvBrd-Mt1tm1Bri Mt2tm1Bri/J (MT-I/II KO) mice and background-matched wild type (WT) mice were used.ResultsBy using a mitochondrial superoxide indicator (MitoSOX Red), lactate dehydrogenase (LDH) release, and methyl thiazolyl tetrazolium (MTT) assay, we demonstrated that the decreased relative viability and increased LDH release and mitochondrial superoxide production induced by potassium iodide (100 µM) can be relieved by 300 µM PTU, 30 µM KClO4, or 10 U/L TSH in the thyroid cell suspensions of both MT-I/II KO and WT mice (P<0.05). Compared to the WT mice, a significant decrease in the relative viability along with a significant increase in LDH release and mitochondrial superoxide production were detected in MT-I/II KO mice(P<0.05).ConclusionWe concluded that PTU, KClO4, or TSH relieved the mitochondrial oxidative stress induced by high concentrations of iodide in the thyroids of both MT-I/II KO and WT mice. MT-I/II showed antioxidant effects against high concentrations of iodide-induced mitochondrial superoxide production in the thyroid.