Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma.

BACKGROUND: We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma. METHODS: Raw264.7 cells were harvested to extract EVs for the preparation of ICG/PTX@RGE-EV by electroporation and click chemistry. We evaluated the success of modifying Neuropilin-1 targeting peptide (RGE) on the EV membrane of ICG/PTX@RGE-EV using super-resolution fluorescence microscopy and flow cytometry. Spectrophotometry and high performance liquid chromatography (HPLC) were implemented for qualitative and quantitative analysis of the ICG and PTX loaded in EVs. Photothermal properties of the vesicles were evaluated by exposing to 808-nm laser light. Western blot analysis, cell counting kit 8 (CCK-8), Calcein Acetoxymethyl Ester/propidium iodide (Calcein-AM/PI) staining, and flow cytometry were utilized for assessing effects of vesicle treatment on cellular behaviors. A nude mouse model bearing glioma was established to test the targeting ability and anti-tumor action of ICG/PTX@RGE-EV in vivo. RESULTS: Under exposure to 808-nm laser light, ICG/PTX@RGE-EV showed good photothermal properties and promotion of PTX release from EVs. ICG/PTX@RGE-EV effectively targeted U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis in U251 cells through chemotherapy combined with hyperthermia. The anti-tumor function of ICG/PTX@RGE-EV was confirmed in the glioma mice via increased accumulation of PTX in the ICG/PTX@RGE-EV group and an increased median survival of 48 days in the ICG/PTX@RGE-EV group as compared to 25 days in the PBS group. CONCLUSION: ICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia.

Porf-2 Inhibits Tumor Cell Migration Through the MMP-2/9 Signaling Pathway in Neuroblastoma and Glioma.

Tumor migration and invasion are key pathological processes that contribute to cell metastasis as well as treatment failure in patients with malignant tumors. However, the mechanisms governing tumor cell migration remain poorly understood. By analyzing the tumor-related database and tumor cell lines, we found that preoptic regulatory factor-2 (Porf-2) is downexpressed in both neuroblastoma and glioma. Using in vitro assays, our data demonstrated that the expression of Porf-2 inhibits tumor cell migration both in neuroblastoma and glioma cell lines. Domain-mutated Porf-2 plasmids were then constructed, and it was found that the GAP domain, which plays a role in the inactivation of Rac1, is the functional domain for inhibiting tumor cell migration. Furthermore, by screening potential downstream effectors, we found that Porf-2 can reduce MMP-2 and MMP-9 expression. Overexpression of MMP-2 blocked the inhibitory effect of Porf-2 in tumor cell migration both in vitro and in vivo. Taken together, we show for the first time that Porf-2 is capable of suppressing tumor cell migration via its GAP domain and the downregulation of MMP-2/9, suggesting that targeting Porf-2 could be a promising therapeutic strategy for nervous system tumors.

The levels of NF-κB p50 and NF-κB p65 play a role in thyroid carcinoma malignancy in vivo.

Background To investigate the relationship between the levels of nuclear factor (NF)-κB p50 and NF-κB p65 and tumour characteristics in patients with thyroid carcinoma. Methods This prospective study enrolled consecutive patients with thyroid carcinoma. Tumour samples were collected and the levels of NF-κB p50 and NF-κB p65 protein and mRNA were measured using immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Results A total of 73 patients with thyroid carcinoma were included in the study (20 males; 53 females; mean ± SD age, 44.8 ± 12.7 years, range, 18-76 years). There were no significant differences in sex, age and pathological type between the NF-κB p50 positive group and the NF-κB p50 negative group, but tumour diameter and lymph node metastasis were significantly higher in the NF-κB p50 positive group compared with the NF-κB p50 negative group. Similar findings were observed for NF-κB p65. The levels of NF-κB p50 were positively correlated with NF-κB p65 in samples of thyroid carcinoma ( rs = 0.653). Conclusion The levels of NF-κB p50 and NF-κB p65 in samples of thyroid carcinoma were positively associated with tumour diameter and the presence of lymph node metastasis.

[Effect of acupuncture treatment of relieving depression and regulating mind on insomnia accompanied with depressive disorders].

OBJECTIVE: To compare the therapeutic effects of insomnia accompanied with depressive disorders treated by acupuncture of relieving depression and regulating mind and oral administration of Trazodone. METHODS: Sixty-five cases were randomly divided into a acupuncture group (33 cases) and western medication group (32 cases). In acupuncture group, Shenmen (HT 7), Baihui (CV 20), Hegu (LI 4) and Taichong (LR 3) were selected. In western medication group, Trazodone was applied with oral administration for 4 weeks. The curative effect comparison was carried on by Pittsburgh Sleep Quality Index (PSQI), Self-Rating Depression Scale (SDS), and Side Effect Rating Scale (SERS) of Asberg. RESULTS: The cured and markedly effective rate of 72.7% (24/33)in acupuncture group was superior to that of 46.8% (15/32) in western medication group; after treatment, the scores of all items and the total cumulative scores of PSQI and SDS of both groups were reduced (P < 0.01, P < 0.05), of which, the sleep quality and daytime function evaluation in acupuncture group reduced more obviously than those in western medication group (both P < 0.05); the SERS scores of Asberg in western medication group were higher than those in acupuncture group. CONCLUSION: Acupuncture treatment of relieving depression and regulating mind is superior to Trazodone with oral administration for sleep quality and daytime function, with milder adverse reactions.

[Clinical study on "Jin's three-needling" in treatment of generalized anxiety disorder].

OBJECTIVE: To study the clinical effect of "Jin's three-needling" in the treatment of generalized anxiety disorder. METHODS: Fifty-eight patients with generalized anxiety were randomly assigned to two groups equally, the medication group treated with anti-anxiety drugs and the acupuncture group with "Jin's three-needling". The treatment course was 6 weeks. The clinical effects were evaluated with Hamilton anxiety scale (HAMA), clinical global impression (CGI), and treatment emergent symptom scale (TESS) before treatment and at the end of 2nd, 4th, 6th week of the treatment course. The concentration of 5-hydroxytryptamine (5-HT) in platelet, and plasma levels of corticosterone (CS) and adrenocorticotropic hormone (ACTH) were measured with high performance liquid chromatography-electrochemical detection (HPLC-ED) method before and after treatment. RESULTS: The clinical effects in the two groups were equivalent, while the adverse reaction found in the acupuncture group was less than that in the medication group (P < 0.05). The platelet concentration of 5-HT and plasma ACTH level decreased significantly in both groups after treatment with insignificant difference between the group (P < 0.05). The plasma CS level had no obvious change in the two groups after treatment as compared with that before treatment respectively. CONCLUSION: "Jin's three-needling" shows similar curative effect on generalized anxiety to routine Western medicine but with less adverse reaction, which may be realized through regulating the platelet 5-HT concentration and plasma ACTH level.