Engineering Nanomedicine for Non-Viral RNA-Based Gene Therapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common type of malignant tumor of the central nervous system, characterized by aggressiveness, genetic instability, heterogenesis, and unpredictable clinical behavior. Disappointing results from the current clinical therapeutic methods have fueled a search for new therapeutic targets and treatment modalities. GBM is characterized by various genetic alterations, and RNA-based gene therapy has raised particular attention in GBM therapy. Here, we review the recent advances in engineered non-viral nanocarriers for RNA drug delivery to treat GBM. Therapeutic strategies concerning the brain-targeted delivery of various RNA drugs involving siRNA, microRNA, mRNA, ASO, and short-length RNA and the therapeutical mechanisms of these drugs to tackle the challenges of chemo-/radiotherapy resistance, recurrence, and incurable stem cell-like tumor cells of GBM are herein outlined. We also highlight the progress, prospects, and remaining challenges of non-viral nanocarriers-mediated RNA-based gene therapy.

An unusual colonic mass in a phlebosclerosis patient.

A 47-year-old man with idiopathic mesenteric phlebosclerosis presented to our hospital because of a 2-month history of diarrhea and edema of both lower limbs. Contrastenhanced abdominal computed tomography (CT) showed a 2-cm mass of mixed density in the ascending colon. On coloscopy, a solid, ulcerated, semi-pedunculated, lobulated protruding mass of 3.5×3.5×1.5 cm was observed and removed with hot snare polypectomy. Histologic examination demonstrated a hamartomatous polyp with normal epithelium and an inflammatory infiltrate with dilated, mucus-filled cystic glands in the lamina propria, indicating a juvenile polyp.

Identification of hub genes and signaling pathways related to gastric cells infected by Helicobacter pylori.

BACKGROUND: Helicobacter pylori is a pathogen involved in several gastroduodenal diseases, whose infection mechanisms have not been completely confirmed. To study the specific mechanism of gastropathy caused by H. pylori, we analyzed the gene microarray of gastric mucosa and gastric cells infected by H. pylori through bioinformatics analysis. METHODS: We downloaded GSE60427 and GSE74492 from the Gene Expression Omnibus (GEO) database, screened differentially expressed genes (DEGs), and identified the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) through R software. The Search Tool for the Retrieval of Interacting Genes (STRING) was applied to establish a protein-protein interaction (PPI) network and Cytoscape was used to identify the top seven hub genes. Besides, we also constructed the gene-microRNA(gene-miRNA) interaction through the miRTarBase v8.0 database by using the NetworkAnalyst tool. RESULTS: One hundred and fifteen DEGs were screened out, with 54 genes up-regulated and 61 genes down-regulated, among which seven hub genes, including "IGF1R," "APOE," "IRS1," "ATF3," "LCN2," "IL2RG," and "PI3," were considered as the main regulatory proteins in gastric cells when infected by H. pylori. CONCLUSION: In this study, hub genes and related signal enrichment pathways of gastropathy infected by H. pylori were analyzed through bioinformatics analysis based on the GSE60427 and GSE74492 datasets.

[Analysis on the academic characteristics of tumor treatment reported in Zhenjiu Dacheng].

Zhenjiu Dacheng (Compendium of Acupuncture and Moxibustion) contains a large number of acupuncture medical cases, involving a variety of illnesses, and more cases of the treatment of cancer. The medical cases in Compendium of Acupuncture and Moxibustion point out that the tumor is a tangible evil, and its pathological factors are often regarded as sputum. It should be diagnosed and treated early, and it is easy to be dangerous if delayed. Acupuncture treatment should be based on the treatment of tumor itself, in the consideration of consolidating the root and cultivating the primary, treatment should be clear about the condition of the disease, pay attention to the timing of acupuncture, selecting correctly the reinforcing or reducing technique, emphasizing the use of moxibustion. The academic characteristics of Compendium of Acupuncture and Moxibustion medical treatment of tumors have had a profound impact on later generations, and it is still of great significance for guiding clinical acupuncture treatment of tumor diseases today.

The Association of Vitamin D Receptor Gene Polymorphism with Lung Cancer Risk: An Update Meta-analysis.

The association between vitamin D receptor (VDR) genetic polymorphism and lung cancer risk has been evaluated by the previous meta-analyses. Due to the emergence of novel studies and inappropriate inclusion of overlapping populations, an updated meta-analysis on recent evidences is necessarily needed. We comprehensively searched databases of PubMed, Web of Science and Chinese National Knowledge Infrastructure and finally obtained 7 eligible studies according to the inclusion criteria. Four positions on VDR gene, namely ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810) and TaqI (rs731236), were considered in this investigation. Data pooling found no significant association of lung cancer risk with ApaI or FokI. In contrast, it was indicated that the BsmI A allele was negatively related to the lung cancer risk, compared with the G allele (OR = 0.51, 95% CI = 0.33-0.79). Individuals with BsmI AA (OR = 0.53, 95% CI = 0.26-1.11) and AG genotypes (OR = 0.46, 95% CI = 0.30-0.71) showed decreased risk of lung cancer, compared with those of GG genotype. Regarding the TaqI polymorphism, the T allele carriers were at increased risk of lung cancer (OR = 1.25, 95% CI = 1.04-1.50). Compared with the TaqI TC+CC genotype, the TT genotype was positively associated with lung cancer risk (OR = 1.42, 95% CI = 1.11-1.82). No publication bias was identified in any of the analysis. In conclusion, VDR genetic polymorphism may be correlated to lung cancer risk. Given limited number of the included studies, more observations are warranted to draw a safer conclusion.

[Comparative experiment on nanoparticle-induced toxicity in human vascular endothelial cells].

OBJECTIVE: To compare the toxic effects of three different particles on vascular endothelial cells, and to investigate the influences of particle composition and sizes on the cardiovascular toxic effects. METHODS: Nano-SiO2 particles, nano-TiO2 particles, and standard quartz particles were selected as the test substances, and the nano-TiO2 particles and standard quartz particles were used as composition controls and size controls, respectively. The human umbilical vein endothelial cells were exposed to different doses (5.0, 10.0, 20.0, 40.0 µg/ml) of the three particles as well as particle-free DMEM medium (0 µg/ml dust) for 24 h. Then, the culture supernatants were collected, and the activities of lactic dehydrogenase (LDH) and total superoxide dismutase (SOD) as well as the releases of NO, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. RESULTS: Compared with those of 0 µg/ml dose group, the LDH activities of all nano-SiO2 groups, 10.0, 20.0, and 40.0 µg/ml nano-TiO2 groups, and 10.0, 20.0, and 40.0 µg/ml standard quartz groups were significantly increased (P < 0.01); the SOD activities of 5.0, 10.0, and 20.0 µg/ml nano-SiO2 groups, 40.0 µg/ml nano-TiO2 group, and 20.0 and 40.0 µg/ml standard quartz groups were significantly increased (P < 0.05), but that of the 40.0 µg/ml nano-SiO2 group was significantly decreased (P < 0.01); the TNF-α releases of 10.0, 20.0, and 40.0 µg/ml nano-SiO2 groups, all nano-TiO2 groups, and 40.0 µg/ml standard quartz group were significantly increased (P < 0.01); the IL-6 releases of 10.0, 20.0, and 40.0 µg/ml nano-SiO2 groups, 20.0 and 40.0 µg/ml nano-TiO2 groups, and 40 µg/ml standard quartz group were significantly increased (P < 0.01). When the dust doses were 5.0, 10.0, 20.0, and 40.0 µg/ml, the LDH activities of nano-SiO2 groups were significantly higher than those of standard quartz groups (P < 0.05); when the dust doses were 10.0, 20.0, and 40.0 µg/ml, the LDH activities of nano-TiO2 groups were significantly lower than those of standard quartz groups (P < 0.05). When the dust doses were 5.0, 10.0, 20.0, and 40.0 µg/ml, the SOD activities of nano-SiO2 groups were significantly higher than those of standard quartz groups (P < 0.01); when the dust dose was 20 µg/ml, the SOD activity of nano-TiO2 group was significantly higher than that of standard quartz group (P < 0.01). When the dust doses were 5.0, 10.0, 20.0, and 40.0 µg/ml, the TNF-α releases of nano-SiO2 groups were significantly higher than those of standard quartz groups (P < 0.01); when the dust doses were 5.0 and 10.0 µg/ml, the TNF-α releases of nano-TiO2 groups were significantly higher than those of standard quartz groups (P < 0.01). When the dust doses were 5.0, 10.0, 20.0, and 40.0 µg/ml, the IL-6 releases of nano-SiO2 groups were significantly higher than those of standard quartz groups (P < 0.05); when the dust doses were 20 and 40 µg/ml, the IL-6 releases of nano-TiO2 groups were significantly higher than those of standard quartz groups (P < 0.05). CONCLUSION: All the three particles are able to exert certain toxic effects on vascular endothelial cells. Nano-SiO2 particles have the most toxic effects, and nano-TiO2 particles and standard quartz particles show uncertain effects. The toxicity of particles is linked to their composition and sizes.

Acaricidal activity of DHEMH, derived from patchouli oil, against house dust mite, Dermatophagoides farinae.

This study characterized the acaricidal activity of constituents of patchouli oil extracted from (Pogostemon cablin (Blanco) BENTH) against the house dust mite, Dermatophagoides farinae. A new compound, 2-(1,3-dihydroxy-but-2-enylidene)-6-methyl-3-oxo-heptanoic acid (DHEMH), was isolated from patchouli oil and characterized by (1)H-NMR, (13)C-NMR, LC-MS and elemental analysis (EA). This active component was identified as the hydrolysate of pogostone. Fifteen other constituents found in patchouli oil were also identified by GC-MS, including patchouli alcohol and pogostone. LD(50) studies carried out over 24 h using contact toxicity tests identified DHEMH as the most toxic compound to D. farinae (2.04 µg/cm(2)), followed by patchouli oil (6.11 µg/cm(2)), benzyl benzoate (BP) (9.31 µg/cm(2)) and dibutyl phthalate (DBP) (58.52 µg/cm(2)). In vapor phase toxicity tests, all of these compounds were more effective in closed than open containers, indicating that the most efficient mode of delivery for these compounds is the vapor phase. These results indicate that DHEMH and patchouli oil merit further study as potential agents for the control of D. farinae.