Ribonuclease A Family Member 2 Promotes the Malignant Progression of Glioma Through the PI3K/Akt Signaling Pathway.

The treatment of patients with glioma still faces many difficulties. To further optimize treatment, it is necessary to identify more accurate markers as treatment targets and predict prognostic indicators. RNASE2 was identified as a differentially expressed gene (DEG) in glioma tissues using bioinformatics analysis. In glioma microarrays, 31.21% (54/173) and 68.79% (119/173) patients showed low and high RNASE2 protein expression levels, respectively. RNASE2 protein levels were considerably correlated with age, WHO grade, relapse, and death. Both mRNA and protein levels were associated with the overall survival of patients with glioma. To investigate the role of RNASE2, it was overexpressed or silenced in glioma cells. RNASE2 overexpression promoted cell proliferation, migration, and invasion. In addition, its overexpression promoted the growth of subcutaneous tumors and lung metastasis of glioma cells. Key protein levels in the PI3K/Akt signaling pathway were upregulated by RNASE2 overexpression. In contrast, RNASE2 knockdown had the opposite effects. Furthermore, LY294002 blocked the effects of RNASE2 on the cell function of glioma cells. In conclusion, RNASE2 is a novel marker associated with the diagnosis and prognosis of patients with glioma, and it promotes the malignant progression of gliomas through the PI3K/Akt signaling pathway.

Critical roles of cytokine storm and secondary bacterial infection in acute kidney injury development in COVID-19: A multi-center retrospective cohort study.

Acute kidney injury (AKI) may develop in patients with coronavirus disease 2019 (COVID-19) and is associated with in-hospital death. We investigated the incidence of AKI in 223 hospitalized COVID-19 patients and analyzed the influence factors of AKI. The incidence of cytokine storm syndrome and its correlation with other clinicopathologic variables were also investigated. We retrospectively enrolled adult patients with virologically confirmed COVID-19 who were hospitalized at three hospitals in Wuhan and Guizhou, China between February 13, 2020, and April 8, 2020. We included 124 patients with moderate COVID-19 and 99 with severe COVID-19. AKI was present in 35 (15.7%) patients. The incidence of AKI was 30.3% for severe COVID-19 and 4.0% for moderate COVID-19 (p < 0.001). Furthermore, cytokine storm was found in 30 (13.5%) patients and only found in the severe group. Kidney injury at admission (odds ratio [OR]: 3.132, 95% confidence interval [CI]: 1.150-8.527; p = 0.025), cytokine storm (OR: 4.234, 95% CI: 1.361-13.171; p = 0.013), and acute respiratory distress syndrome (ARDS) (OR: 7.684, 95% CI: 2.622-22.523; p < 0.001) were influence factors of AKI. Seventeen (48.6%) patients who received invasive mechanical ventilation developed AKI, of whom 64.7% (11/17) died. Up to 86.7% of AKI patients with cytokine storms may develop a secondary bacterial infection. The leukocyte counts were significantly higher in AKI patients with cytokine storm than in those without (13.0 × 109/L, interquartile range [IQR] 11.3 vs. 8.3 × 109/L, IQR 7.5, p = 0.005). Approximately 1/6 patients with COVID-19 eventually develop AKI. Kidney injury at admission, cytokine storm and ARDS are influence factors of AKI. Cytokine storm and secondary bacterial infections may be responsible for AKI development in COVID-19 patients.

Evaluation of the thyroid characteristics of patients with growth hormone-secreting adenomas.

BACKGROUND: Acromegaly is highly associated with thyroid disorders. However, the clinical characteristics of thyroid nodules in individuals with acromegaly who present with thyroid diseases have not been completely elucidated. METHODS: Overall, 134 consecutive participants with growth hormone (GH)-secreting adenoma (n = 67) and non-functioning (NF) pituitary adenoma (n = 67) were recruited from the outpatient and inpatient patient department of The First Affiliated Hospital, Jinan University from August 2015 to August 2017. Thyroid ultrasonography was performed using an ultrasound system. The cytopathological results of fine-needle aspiration biopsy were analyzed by a pathologist according to the Bethesda system. Twenty-one patients with GH-secreting adenoma and thyroid disease underwent transsphenoidal pituitary adenoma resection and were followed up for 1 year. RESULTS: The prevalence of thyroid disease increased in the GH-secreting adenoma group compared with that in the NF pituitary adenoma group. The number of hypoechoic, isoechogenic, heterogeneous, and vascular thyroid nodules increased in patients with GH-secreting adenoma plus thyroid disease compared with that in patients with NF pituitary adenoma plus thyroid disease. Finally, we found significant decreases in the morphology of solid nodules and significant increases in the morphology of cystic nodules after surgery compared with those before surgery in the cured group. Moreover, the numbers of heterogeneous and vascular thyroid nodules decreased significantly after surgery compared with those before surgery in the cured group. However, the characteristics of the thyroid nodules did not change after surgery compared with those before surgery in the non-cured group. CONCLUSIONS: The numbers of hypoechoic, isoechoic, heterogeneous, and vascular thyroid nodules increased in patients with GH-secreting adenomas. In these patients, surgery resulted in significant changes from solid to cystic nodules and also reduced the numbers of heterogeneous and vascular thyroid nodules.

Downregulation of Pygopus 2 inhibits vascular mimicry in glioma U251 cells by suppressing the canonical Wnt signaling pathway.

Gliomas are the most common type of malignant primary brain tumor, and the Wnt signaling pathway is associated with glioma malignancy. Pygopus protein plays an important role in developmental brain patterning, and has been identified to be a component of the Wnt signaling pathway. In the present study, the Pygopus 2 (Pygo2) protein was examined in 80 glioma tissue samples. Short hairpin (sh)RNA-Pygo2 was transfected into glioma U251 cells, and the cell proliferation, colony formation and bromodeoxyuridine (BrdU) incorporation were analyzed. Western blot analysis and reverse transcription-polymerase chain reaction were used to detect the expression of Pygo2. A vascular mimicry assay was performed to examine the vascular mimicry of U251 cells. A luciferase reporter assay was used to detect the ß-catenin/Wnt system. The cyclin D1 protein was also detected using western blot analysis. The results demonstrated that inhibition of the expression of Pygo2 significantly triggered the decrease of cell proliferation, colony formation and BrdU incorporation compared with the cells treated with scramble control shRNA (shRNA-Scr). shRNA-Pygo2 transfection was found to inhibit vascular-mimicry and block the Wnt signaling pathway compared to the cells transfected with shRNA-Scr. The transfection of shRNA-Pygo2 also decreased the expression of the Wnt target gene cyclin D1. In conclusion, shRNA-Pygo2 suppressed glioma cell proliferation effectively and inhibited vascular mimicry by inhibiting the expression of cyclin D1 in the canonical Wnt/ß-catenin pathway in brain glioma cells.

Tetra-sulfonate phthalocyanine zinc-bovine serum albumin conjugate-mediated photodynamic therapy of human glioma.

BACKGROUND: Glioma is the most common brain malignancy with poor prognosis. The current treatments for gliomas are mainly based on surgery, chemotherapy, and radiotherapy, which exhibit limited efficacy. Photodynamic therapy (PDT) using photosensitizers has been applied to glioma therapy. However, different photosensitizers usually lead to different therapeutic effects and adverse reactions. OBJECTIVE: This study investigates the anti-tumor effect of photosensitizer ZnPcS4-BSA in xenograft glioma tumors. METHODS: The xenograft glioma tumor model was established by inoculating nude mice with U251 cells. Tumor growth was evaluated by tumor volume, weight, and inhibition rate. Cell apoptosis was evaluated using TUNEL staining. Vascular endothelial growth factor (VEGF) expression and microvessel density were measured by immunohistochemistry. RESULTS: Significant decreases in tumor volume and weight as well as significant increases in tumor inhibition rate, cell apoptosis, VEGF expression, and microvessel density were observed in mice in the low- and high-dose PDT groups compared to the control, irradiation alone, and photosensitizer alone groups. No significant difference in cytotoxicity was observed between control group and photosensitizer alone group. Photosensitizer ZnPcS4-BSA significantly inhibited xenograft glioma tumor growth through induction of apoptosis. CONCLUSION: PDT using ZnPcS4-BSA may be effective for the therapy of gliomas.

Endovascular treatment for wide-necked intracranial aneurysms with the Enterprise stent.

BACKGROUND: The development of self-expanding stents dedicated to intracranial use has significantly widened the applicability of endovascular therapy to many intracranial aneurysms OBJECTIVE: To report the angiographic and clinical outcomes of wide-necked intracranial aneurysms treated using the Enterprise stent. MATERIAL AND METHODS: Forty-six patients with 50 wide-necked and fusiform aneurysms (19 aneurysms with dissections), admitted between June 2009 and December 2010, were treated using Enterprise stents. Demographic information, procedural data, and technical complication were reviewed. Angiographic and clinical outcomes were evaluated at a 9.1-month follow-up. RESULTS: Stent deployment was successful in all the 50 lesions, and additional coil embolization was performed in 48. Complete or near-complete occlusion immediately after stent deployment was achieved in 44 aneurysms, whereas, no immediate coil embolization was chosen in two cases. There was one (2%) procedure-related complication, which resulted in death. At mean 9.1-month follow-up, the result was good (GOS ≤2) in 45 patients. Angiographic recurrences arose in two cases, one of which was re-treated completely. CONCLUSIONS: The Enterprise stent is very useful for endovascular embolization of wide-necked intracranial aneurysms, because it is easy to navigate and place precisely. The overall morbidity and mortality rates are low.

In vitro photodynamic therapy on human U251 glioma cells with a novel photosensitiser ZnPcS4-BSA.

This article reports the phototoxicity effects of a novel photosensitiser ZnPcS4-BSA on human U251 glioma cells in vitro. The cellular uptake of ZnPcS4-BSA by U251 glioma cells was quantified by UV-spectra, and the optimal incubation time was determined. Human U251 glioma cells were incubated in ZnPcS4-BSA of various concentrations, and received laser irradiation of different energy densities. Cell survival rates were measured by CCK-8 assay. Flow cytometer was used to detect apoptosis. Expression of vascular endothelial growth factor (VEGF) gene was detected by real-time PCR in U251 cells after photodynamic therapy (PDT), and ß-actin was used as an internal standard. The normal U251 cells severed as controls. Results indicate that the uptake of ZnPcS4-BSA by U251 glioma cells reaches maximum after incubation for 4 hours. ZnPcS4-BSA with different concentrations without light irradiation has no significant effects on cell survival rates. Without ZnPcS4-BSA incubation, cell survival rate of high-dose group (400 J/cm(2)) is the lowest, whereas no significant difference has been found between any other two groups. At laser irradiation of 150 J/cm(2), inhibition rates of the cells increase with ZnPcS4-BSA concentration, and half-inhibitory concentration (IC50) is 0.16 µmol/L. Apoptosis rate of the cells after PDT is significantly higher than that of the control group (p < 0.01). The VEGF expression in the cells increases 5.616 times after PDT. The novel ZnPcS4-BSA is a good photosensitiser for PDT towards U251 glioma cells. The ZnPcS4-BSA based PDT can induce effective apoptosis.