Growth inhibition of subcutaneous tumor with glioma cells in nude mice by silencing TLR4.

This study investigated the regulatory impact of Toll-like receptor 4 (TLR4) gene on glioma cell proliferation and apoptosis, elucidating the molecular mechanisms underlying TLR4-induced growth inhibition in vivo. U-87MG-Sh and U-87MG-NC cells, with silenced TLR4 and negative control plasmid respectively, were established. Eighteen nude mice, divided into transfection, negative control, and blank control groups, were inoculated with corresponding cells. Over four weeks, the transfection group exhibited significantly reduced tumor growth rates, smaller mass and volume, and lower growth activity compared to controls. Histological analysis revealed sparse tumor cells, increased fibrous connective tissue, and slower angiogenesis in the transfection group. Flow cytometry demonstrated a lower proliferation index and increased G0/1 cell count in the transfection group. mRNA levels of TLR4, NF-κB, and CyclinD1 were significantly lower in the transfection group. TLR4 silencing correlated with U-87MG cell proliferation regulation, growth inhibition, NF-κB and CyclinD1 modulation, and induction of cell cycle arrest and apoptosis. These findings suggest TLR4 as a potential gene therapy target for glioma.

Graphene oxide and Lambda exonuclease assisted screening of L-carnitine aptamers and the site-directed mutagenesis design of C-rich structure aptamer.

In this study, Graphene Oxide (GO) was used to screen the binding with the aptamers of L-carnitine chiral enantiomers. The ssDNA library was prepared by the method of Lambda exonuclease. In addition, a simple casing device was designed to improve the purification and recovery efficiency of the small ssDNA fragments in the process of screening. Finally, more than 160,000 aptamer sequences were obtained by high-throughput sequencing. We determined the strongest affinity aptamer sequence, CA04, by the Resonance Rayleigh scattering (RRS) technology. We also analyzed the key binding sites (in the 16th position case) of the truncated aptamer sequence CAD10. Interestingly, we found that aptamer CA10 and CA06 were both C-rich bases through sequence alignment and analysis, and the aptamer CA10 was confirmed that the CA10 and CA06 were formed under acidic conditions (pH 4.5) by CD spectrum and ESI-MS analysis. The interaction between gold nanoparticles (AuNPs) and functionalized aptamer CA10 was analyzed. We used Site-directed mutagenesis design and QGRS Mapper to optimize aptamer CA10, where an optimal aptamer CA10-03 were obtained after affinity analysis. It is also proved to be an effective method to obtain stronger affinity aptamer. Meanwhile, Native-PAGE and UV spectrum analysis were performed on the mutation sequences, and the interaction with ThT was analyzed. Finally, it is hoped that my study can provide help for later identification and detection of L-carnitine.

Serum levels of miR-19b and miR-146a as prognostic biomarkers for non-small cell lung cancer.

MicroRNA (miRNA) is a type of small non-coding RNA molecule that has important roles in cancer initiation, promotion and progression by negatively regulating gene expression. In this study, we explored the role of miRNAs in the prognosis of patients with non-small cell lung cancer (NSCLC). The miRNA expression profiles were determined in 5 pairs of NSCLC and paracancerous tissues (3 adenocarcinomas and 2 squamous cell carcinomas). Aberrantly expressed miRNAs were validated by quantitative real-time PCR (qRT-PCR) in 61 pairs of NSCLC and paracancerous tissues. Differentially expressed miRNAs were further analyzed in sera from 94 healthy subjects and 94 advanced NSCLC patients receiving platinum-based chemotherapy. Three miRNAs (miR-19b, miR-146a, and miR-223) were significantly dysregulated in NSCLC tissues (P < 0.05). High miR-19b and low miR-146a expression in NSCLC tissues were associated with higher TNM stage, lymph node metastasis and poorer survival (P < 0.05). The serum levels of miR-19b in NSCLC patients were significantly higher (P < 0.001), whereas serum levels of miR-146a were significantly lower (P < 0.001), compared with those in controls. Serum levels of miR-19b and miR-146a were associated with overall survival of NSCLC patients (P < 0.05). Patients with low serum level of miR-19b and high serum level of miR-146a achieved a higher overall response rate and longer survival time (P < 0.05). These data suggest that miR-19b and miR-146a are potential biomarkers for the prediction of survival and response to chemotherapy in NSCLC.

Observation based climatology Martian atmospheric waves perturbation Datasets.

The Martian atmospheric waves perturbation Datasets (MAWPD) version 2.0 is the first observation-based climatology dataset of Martian atmospheric waves. It contains climatology-gridded temperature, gravity waves, and tides spanning the whole Martian year. MAWPD uses the Data INterpolating Empirical Orthogonal Functions method (DINEOF) reconstruction method for data assimilation with the observational data from the Mars Global Surveyor (MGS), Mars Reconnaissance Orbiter (MRO), Mars Atmosphere and Volatile EvolutioN (MAVEN), Mars Pathfinder (MP), Mars Phoenix Lander (MPL), Mars Exploration Rover (MER) and Mars Express (MEX) temperature retrievals. The dataset includes gridded fields of temperature (Level 1 data) as well as the physical quantities of GWs (Level 2 data, amplitude, and potential energies), SPWs and tides (Level 2 data, amplitude, and phase). The MAWPD, based entirely on multiple reliable observations, provides climatological background atmospheric information of temperature and wave disturbances on Mars. The dataset is not only useful for observation-based scientific studies concerning Martian atmospheric waves, e.g., circulation, dust storms, and wave excitation mechanism, but also for cross-validating with model-based datasets or model results.

Effect of Kang'ai Injection on serum level of soluble interleukin-2 receptor and vascular endothelial growth factor in patients with esophageal carcinoma during radiotherapy.

OBJECTIVE: To observe the effect of Kang'ai Injection (KAI) on serum level of soluble interleukin-2 receptor (slL-2R) and vascular endothelial growth factor (VEGF) in patients with esophageal carcinoma (EC) during radiotherapy (RT), and to investigate its synergistic effect with RT and its influence on immunological function of the body. METHODS: One hundred and seventy patients with EC, who had missed the chance of surgical operational therapy, were assigned to the treated group (90 cases) and the RT group (80 cases), and at the same time a control group consisting of 80 inpatients without tumors was set up. Patients in the RT group were treated with RT alone but KAI was given additionally to those in the treated group, with 50 ml given once per day via intravenous dripping, 15 days as one course, and 2 courses administered in total. The immediate therapeutic efficacy and changes of serum slL-2R and VEGF levels were observed, and the effect of KAI on patients' quality of life (QOF) was evaluated by Karnofsky scoring. RESULTS: In 16 patients of the treated group it was completely remission (CR), in 54 partially remission (PR), in 18 it was stabilized disease (SD) and in 2 progressive disease (PD), with the total effective rate (CR + PR) as 77.8%, while in those of the control group it was 12, 46, 18, 4 and 72.5%, respectively, the immediate therapeutic efficacy in the treated group was somewhat better than that in the RT group, but showed no statistical significance (P>0.05). Serum levels of slL-2R and VEGF in all the patients before treatment were higher than those in the control group, which were decreased after treatment in both groups ( P<0.05), but the improvement in the treated group was better than that in the RT group, showing significant difference (P<0.05), and patients' QOF improved more significantly in the former as well (62.2% vs 40.0%, P< 0. 05). CONCLUSION: KAI in combination with RT in treating patients with EC could enhance the immunological function of patients, improve their QOF and enhance their sensitivity to RT.

[RNA Interference targeting GRP75 decreases cisplatin resistance in human lung adenocarcinoma cell].

BACKGROUND AND OBJECTIVE: GRP75, a member of HSPs which is overexpressed in some resistant cancer cells, is a molecular chaperone mainly located in mitochondrial membrane. The aim of this study is to investigate the role of GRP75 on the resistant mechanisms of cancer cells by downregulating GRP75 expreesion via RNAi approach. METHODS: Cisplatin-resistant cell A549/CDDP was established from their parental human lung adenocarcinoma cell line A549 by combining gradually increasing concentrations of cisplatin with high dosage impact. The shRNA for GRP75 was transfected into A549 and A549/CDDP cells by lentivirus. Western blot and methyl thiazolyl tetrazolium (MTT) assay were applied to detect the influence of silencing GRP75 expression on sensitivity of the cells to cisplatin. RESULTS: The infection rate of six groups were all over 90%. After infection, the level of expression of GRP75 in both A549 and A549/CDDP were down-regulated (P < 0.05); the level of expression of p53 in A549/CDDP was up-regulated (P < 0.05) and the level of expression of bcl-2 of A549/CDDP was down-regulated (P < 0.05). The resistance index of A549/CDDP before and after infection were 21.52 and 4.14 respectively. CONCLUSIONS: Cisplatin resistance of lung cancer cells is associated with overexpression of GRP75 gene, which could regulate the expressions of p53 and bcl-2.