Inhibition of DEF-p65 Interactions as a Potential Avenue to Suppress Tumor Growth in Pancreatic Cancer.

The limited success of current targeted therapies for pancreatic cancer underscores an urgent demand for novel treatment modalities. The challenge in mitigating this malignancy can be attributed to the digestive organ expansion factor (DEF), a pivotal yet underexplored factor in pancreatic tumorigenesis. The study uses a blend of in vitro and in vivo approaches, complemented by the theoretical analyses, to propose DEF as a promising anti-tumor target. Analysis of clinical samples reveals that high expression of DEF is correlated with diminished survival in pancreatic cancer patients. Crucially, the depletion of DEF significantly impedes tumor growth. The study further discovers that DEF binds to p65, shielding it from degradation mediated by the ubiquitin-proteasome pathway in cancer cells. Based on these findings and computational approaches, the study formulates a DEF-mimicking peptide, peptide-031, designed to disrupt the DEF-p65 interaction. The effectiveness of peptide-031 in inhibiting tumor proliferation has been demonstrated both in vitro and in vivo. This study unveils the oncogenic role of DEF while highlighting its prognostic value and therapeutic potential in pancreatic cancer. In addition, peptide-031 is a promising therapeutic agent with potent anti-tumor effects.

Directional Pumpless Transport of Biomolecules through Self-Propelled Nanodroplets on Patterned Heterostructures.

The surface patterning in natural systems has exhibited appreciable functional advantages for life activities, which serve as inspiration for the design of artificial counterparts to achieve functions such as directional liquid transport at the nanoscale. Here, we propose a patterned two-dimensional (2D) in-plane heterostructure with a triangle-shaped hexagonal boron nitride (hBN) track embedded in graphene nanosheets, which can achieve unidirectional and self-propelled transport of nanodroplets carrying various biomolecules such as DNA, RNA, and peptides. Our extensive MD simulations show that the wettability gradient on the patterned heterostructure can drive the motion of nanodroplet with an instantaneous acceleration, which also permits long-distance transport (>100 nm) at the microsecond time scale. The different behaviors of various types of biomolecules have been further studied systematically within the transporting nanodroplets. These findings suggest that these specially designed, patterned heterostructures have the potential for spontaneous, directional transport of important biomolecules, which might be useful in biosensing, drug delivery, and biomedical nanodevices.

De Novo Evolution of an Antibody-Mimicking Multivalent Aptamer via a DNA Framework.

Multivalent interactions can often endow ligands with more efficient binding performance toward target molecules. Generally speaking, a multivalent aptamer can be constructed via post-assembly based on chemical structural information of target molecules and pre-identified monovalent aptamers derived from traditional systematic evolution of ligands by exponential enrichment (SELEX) technology. However, many target molecules may not have known matched aptamer partners, thus a de novo evolution will be highly desired as an alternative strategy for directed selection of a high-avidity, multivalent aptamer. Here, inspired by the superiority of multivalent interactions between antibodies and antigens, a direct SELEX strategy with a preorganized DNA framework library for an "Antibody-mimicking multivalent aptamer" (Amap) selection to epithelial cell adhesion molecule (EpCAM), a model target protein is reported. The Amap presents a relatively good binding affinity through both aptamer moieties concurrently binding to EpCAM, which has been confirmed by affinity analysis and molecular modeling. Furthermore, dynamic interactions between Amap and EpCAM are directly visualized by magnetic tweezers at the single-molecule level. A nice binding affinity of Amap to EpCAM-positive cancer cells has also been verified, which hints that their Amap-SELEX strategy has the potential to be a new route for de novo evolution of multivalent aptamers.

LncRNA HLA-F-AS1 Enhances the Migration, Invasion and Apoptosis of Glioblastoma Cells by Targeting lncRNA MEG3.

BACKGROUND: Previous studies revealed the oncogenic role of long non-coding RNA (lncRNA) HLA-F-AS1 in colon cancer and breast cancer, while its role in other cancers is unclear. We predicted the direct interaction between HLA-F-AS1 and MEG3, which is a tumor suppressor lncRNA. We then assessed the interaction between HLA-F-AS1 and MEG3 in glioblastoma (GBM). METHODS: The expression levels of HLA-F-AS1 and MEG3 in GBM and paired non-tumor tissues from 60 GBM patients were analyzed by RT-qPCR. Overexpression of HLA-F-AS1 and MEG3 was achieved in GBM cells to explore the interaction between them. The direct interaction between them was confirmed by RNA pull-down assay. The roles of HLA-F-AS1 and MEG3 in cell invasion, migration and apoptosis were explored by Transwell assays and cell apoptosis assay. RESULTS: HLA-F-AS1 was highly expressed, and MEG3 was downregulated in GBM. Overexpression of HLA-F-AS1 reduced the expression levels of MEG3 while overexpression of MEG3 did not alter the expression of HLA-F-AS1. HLA-F-AS1 increased cell migration and invasion, but decreased cell apoptosis. MEG3 played opposite roles and reduced the effects of HLA-F-AS1 on cell behaviors. CONCLUSION: HLA-F-AS1 may sponge MEG3 in GBM cells to promote cell invasion and migration, and to suppress cell apoptosis.

Long non-coding RNA as a potential biomarker for prognosis of glioma: A protocol for systematic review and meta-analysis.

BACKGROUND: The molecular mechanism of Glioma is still unclear, and there are few early diagnostic markers. Therefore, it is urgent to figure out effective preventive measures, active diagnostic methods and rapid treatment measures. In recent years, relevant studies have revealed that long non-coding RNA (lncRNA) is associated with the prognosis of Glioma. However, these results have not been supported by any evidence. Therefore, this study carried out a meta-analysis method to analyze the relationship between lncRNA and the prognosis of Glioma. In addition, bioinformatics analysis was conducted to investigate the mechanism and related pathways of lncRNAs in Glioma. METHODS: We performed a systematic search in electronic databases, including China National Knowledge Infrastructure, Chinese Biomedical literature Database, Chinese Scientific and Journal Database, Wan Fang database, PubMed, EMBASE, Cochrane Library and Web of Science, to investigate the potential association between lncRNA expression and prognostic significance and clinical features in glioma patients. Hazards ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled to estimate the prognosis value of lncRNA by Stata16.0 software. The online tool AnnoLnc was applied to screen the co-expressed gene related to each lncRNA, David was used for gene ontology (GO) analysis and enrichment analysis of the signal pathway, and through Starbase, the possible competitive endogenous RNA network of lncRNAs was constructed. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: This study will provide evidence-based medical evidence for lncRNA, so as to predict the prognosis of Glioma and bioinformatics analysis will provide ideas for the mechanism study on Glioma.

Therapeutic Benefits of Mesenchymal Stromal Cells in a Rat Model of Hemoglobin-Induced Hypertensive Intracerebral Hemorrhage.

Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-1ß and TNF-α). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

Enhanced photocatalytic H2 generation on cadmium sulfide nanorods with cobalt hydroxide as cocatalyst and insights into their photogenerated charge transfer properties.

Cobalt hydroxide/cadmium sulfide composite was prepared using an easy coprecipitation strategy. The field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) confirmed that Co(OH)2 nanometer particles were modified on CdS. Even without noble-metal cocatalyst, the photocatalytic H2 evolution over CdS after Co(OH)2 loaded was evidently increased. The most excellent Co(OH)2 of 6.8 mol %, resulted in a H2 generation rate of 61 µmol h(-1) g(-1), which exceeded that of pure CdS by a factor of 41 times. Surface photovoltage (SPV) and surface photocurrent (SPC) investigations revealed that the photogenerated electrons could be captured by the loaded Co(OH)2 nanoparticles. The interface formed between Co(OH)2 and CdS is vital to the enhancement of photocatalytic H2 generation. Electrochemical measurement results indicated that another reason for the enhanced photocatalytic activity of Co(OH)2/CdS catalyst is that Co(OH)2 has outstanding H2 generation activity.

Spontaneous brain activity in chronic smokers revealed by fractional amplitude of low frequency fluctuation analysis: a resting state functional magnetic resonance imaging study.

BACKGROUND: Nicotine is primarily rsponsible for the highly addictive properties of cigarettes. Similar to other substances, nicotine dependence is related to many important brain regions, particular in mesolimbic reward circuit. This study was to further reveal the alteration of brain function activity during resting state in chronic smokers by fractional amplitude of low frequency fluctuation (fALFF) based on functional magnetic resonance imaging (fMRI), in order to provide the evidence of neurobiological mechanism of smoking. METHODS: This case control study involved twenty healthy smokers and nineteen healthy nonsmokers recruited by advertisement. Sociodemographic, smoking related characteristics and fMRI images were collected and the data analyzed. RESULTS: Compared with nonsmokers, smokers showed fALFF increased significantly in the left middle occipital gyrus, left limbic lobe and left cerebellum posterior lobe but decreases in the right middle frontal gyrus, right superior temporal gyrus, right extra nuclear, left postcentral gyrus and left cerebellum anterior lobe (cluster size >100 voxels). Compared with light smokers (pack years ≤ 20), heavy smokers (pack years >20) showed fALFF increased significantly in the right superior temporal gyrus, right precentral gyrus, and right occipital lobe/cuneus but decreased in the right/left limbic lobe/cingulate gyrus, right/left frontal lobe/sub gyral, right/left cerebellum posterior lobe (cluster size >50 voxels). Compared with nonsevere nicotine dependent smokers (Fagerstrom test for nicotine dependence, score ≤ 6), severe nicotine dependent smokers (score >6) showed fALFF increased significantly in the right/left middle frontal gyrus, right superior frontal gyrus and left inferior parietal lobule but decreased in the left limbic lobe/cingulate gyrus (cluster size >25 voxels). CONCLUSIONS: In smokers during rest, the activity of addiction related regions were increased and the activity of smoking feeling, memory, related regions were also changed. The resting state activity changes in many regions were associated with the cumulative amount of nicotine intake and the severity of nicotine dependence.

Is X-linked methyl-CpG binding protein 2 a new target for the treatment of Parkinson's disease.

X-linked methyl-CpG binding protein 2 mutations can induce symptoms similar to those of Parkinson's disease and dopamine metabolism disorders, but the specific role of X-linked methyl-CpG binding protein 2 in the pathogenesis of Parkinson's disease remains unknown. In the present study, we used 6-hydroxydopamine-induced human neuroblastoma cell (SH-SY5Y cells) injury as a cell model of Parkinson's disease. The 6-hydroxydopamine (50 µmol/L) treatment decreased protein levels for both X-linked methyl-CpG binding protein 2 and tyrosine hydroxylase in these cells, and led to cell death. However, overexpression of X-linked methyl-CpG binding protein 2 was able to ameliorate the effects of 6-hydroxydopamine, it reduced 6-hydroxydopamine-induced apoptosis, and increased the levels of tyrosine hydroxylase in SH-SY5Y cells. These findings suggesting that X-linked methyl-CpG binding protein 2 may be a potential therapeutic target for the treatment of Parkinson's disease.