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Background: Glioma is the most common tumor of the central nervous system, which has a high mortality and recurrence rate. Increasing evidence shows that long noncoding RNAs (lncRNA) are closely re...

Inflammation and tissue infiltration by various immune cells play a significant role in the pathogenesis of neurons suffering the central nervous systems diseases. Although brachial plexus root avulsion (BPRA) leads to dramatic motoneurons (MNs) death and permanent loss of function, however, the knowledge gap on cytokines and glial reaction in the spinal cord injury is still existing. The current study is sought to investigate the alteration of specific cytokine expression patterns of the BPRA injured spinal cord during an acute and subacute period. The cytokine assay, transmission electron microscopy, and histological staining were utilized to assess cytokine network alteration, ultrastructure morphology, and glial activation and MNs loss within two weeks post-injury on a mouse unilateral BPRA model. The BPRA injury caused a progressively spinal MNs loss, reduced the alpha-(α) MNs synaptic inputs, whereas enhanced glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule-1 (IBA-1), F4/80 expression in ipsilateral but not the contralateral spinal segments. Additionally, cytokine assays revealed BPRA significantly altered the level of CXCL1, ICAM1, IP10, MCP-5, MIP1-α, and CD93. Notably, the elevated MIP1-α was mainly expressed in the injured spinal MNs. While the re-distribution of CD93 expression, from the cytoplasm to the nucleus, occasionally occurred at neurons of the ipsilateral spinal segment after injury. Overall, these findings suggest that the inflammatory cytokines associated with glial cell activation might contribute to the pathophysiology of the MNs death caused by nerve roots injury.

Citrus fruits are a rich source of vitamin C and phytochemicals and can be an important part of a healthy diet. Citrus is believed to prevent the occurrence or shorten the duration of symptoms of the common cold and influenza, but meta-analysis of vitamin C clinical trial data is inconclusive. We examined whether citrus flavonoids activated antiviral pathways that might explain the perceived efficacy against the common cold and influenza. We found that a citrus bioflavonoid blend augmented NFkB activation in the presence of imiquimod. In addition, the citrus bioflavonoid blend, as well as individual flavonoids found in the blend, activated the interferon-stimulated response element (ISRE). The ability to activate the ISRE appeared to due to the flavonoids’ ability to upregulate expression of the transcription factor interferon regulatory factor 7 (IRF7). Our results suggest that flavonoids from citrus may stimulate antiviral pathways due to their ability to activate the ISRE.

Stimuli-responsive gene delivery vectors based on physiologically triggered structure changing have been recently recognized as a new therapeutic agent for their excellent performance in vivo. Herein, we present an intelligent gene delivery system based on the octa-arginine peptides (R8)-conjugated polyamino acid derivatives noted as PPCRC (PVIm-(PAsp-Cystamine-R8)-Cholesteryl), which processed pH responsive, surface charge-switching, intracellular redox-responsive and enhanced nucleus import of gene together. Due to the imidazole group in the PPCRC backbone, the DNA/PPCRC polyplexes not only exhibited the enhanced buffering capacity in the endosome after endocytosis, but also displayed the reversible surface charge from negative to positive with decreasing the pH value form pH 7.4 to pH 6.5–6.8, which would promote the cell membrane binding and cellular uptake. The disulfide bond for R8 peptides conjugation in the polymer side chain could be rapidly cleaved under reductive conditions, facilitating DNA release in the cytoplasm. Subsequently, the DNA would be still associated with the R8 peptides, which would promote the intracellular nucleus import of DNA. The luciferase gene expression level of COS-7 cells transfected by DNA/PPCRC polyplexes was almost 2000 folds higher than cells transfected by DNA/PPCC polyplexes (without R8 peptides modification) in growth-arrested cell model. Nearly 10 folds enhanced gene transfection efficiency was found on human bone mesenchymal stem cells (hBMSCs) using the same strategy, which revealed that this intelligent vector can be also utilized in transfection of non-dividing cells. Intravenous injection of the DNA/PPCRC polyplexes also achieved the effective transfection in subcutaneous tumor model. Taken together, PPCRC vector has great potential for both dividing and non-dividing cells transfection and in vivo gene delivery application.

The neuronal mechanisms underlying brachial plexus roots avulsion-induced motoneuron death are unknown. Our previous studies showed that the avulsion induced obvious temporal and spatial expression of both degenerative and regenerative genes in the injured spinal cord tissue. Therefore, we hypothesized that lncRNAs (responsible for epigenetic molecular mechanisms) are altered (resulting in altered gene expression patterns) at days 3 and 14 after avulsion. In the present microarray study, 121 lncRNAs (83 up/38 down) and 844 mRNAs (726 up/118 down) were differentially expressed (ipsilateral vs contralateral) after avulsion. We further used qRT-PCR as a validation tool to confirm the expression patterns of 5 lncRNAs and 5 mRNAs randomly selected from our microarray analysis data. The gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify the critical biological processes and pathways. The noted downregulation of the AF128540 (which targets the nNOS gene) is consistent with the high expression of nNOS protein observed at day 14 post-avulsion. The downregulation of MRAK034299, whose target is the Adra1d gene, is consistent with the downregulation of Adra1d mRNA and protein at days 3 and 14 post avulsion. Immunofluorescence evaluation showed cytoplasmic translocation of ECEL1 after avulsion injury. Moreover, we also found that IL6 and Rac2 are the core genes at days 3 and 14 after unilateral brachial plexus roots avulsion, respectively. Overall, our present data suggest that the altered LncRNAs (avulsion-induced), via unknown epigenetic mechanisms, certainly contribute to the molecular mechanism underpinning motoneuron death or survival. Therefore, the avulsion-induced differentially expressed lncRNAs and mRNAs may offer potential diagnostic and therapeutic targets for BPRA.

Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor 2 (Her2) and cluster determinant 44 (CD44), is one of the most malignant human tumors which causes a high mortality rate due to rapid tumor growth and metastasis. To develop effective therapeutic treatments, a dual-targeting hybrid nanoparticle (NP) system was designed and constructed to deliver the SN38 agent specifically to human solid gastric tumors bearing excessive Her2 and CD44. The hybrid NPs consist of a particle core made of the biodegradable polymer PLGA and a lipoid shell prepared by conjugating the AHNP peptides and n-hexadecylamine (HDA) to the carboxyl groups of hyaluronic acid (HA). Upon encapsulation of the SN38 agent in the NPs, the AHNP peptides and HA on the NP surface allow preferential delivery of the drug to gastric cancer cells (e.g., HGC27 cells) by targeting Her2 and CD44. Cellular uptake and in vivo biodistribution experiments verified the active targeting and prolonged in vivo circulation properties of the dual-targeting hybrid NPs, leading to enhanced accumulation of the drug in tumors. Furthermore, the anti-proliferation mechanism studies revealed that the inhibition of the growth and invasive activity of HGC27 cells was not only attributed to the enhanced cellular uptake of dual-targeting NPs, but also benefited from the suppression of CD44 and Her2 expression by HA and AHNP moieties. Finally, intravenous administration of the SN38-loaded dual-targeting hybrid NPs induced significant growth inhibition of HGC27 tumor xenografted in nude mice compared with a clinical antitumor agent, Irinotecan (CPT-11), and the other NP formulations. These results demonstrate that the designed dual-targeting hybrid NPs are promising for targeted anti-cancer drug delivery to treat human gastric tumors over-expressing Her2 and CD44.

Ginkgo biloba, a traditional herbal remedy and a popular functional food is sold commercially in form of a standardized extract for its flavone glycosides content (24%) and terpene lactones (6%). The ginkgo terpene lactones are the unique components of ginkgo leaves unlike the flavone glycosides which are quite common in other botanical extracts. Therefore, flavone glycosides (and their respective aglycones) are the main targets of adulteration of ginkgo extracts to meet the marker levels in the commercially available raw materials in the market. We have investigated the typical quality of a wide variety of commercial ginkgo extracts as well as their potential adulterants. Based on our analytical results we have classified the commercially available extracts of G. biloba into three categories such as authentic, intermediate and adulterated/spiked. A combination of qualitative determination of the unhydrolyzed extracts by phytochemical fingerprinting as well as typical quantitative analysis for total flavone glycosides including Q/K/I (quercetin/kaempferol/isorhamnetin) peak area ratio on hydrolyzed samples is recommended to establish/track the authenticity of the available extracts for formulation purposes.

Ginkgo biloba is the only genus and species of the botanical family Ginkgoaceae, and is one of the best-known examples of a living fossil. This family of prehistoric trees once included several species which grew in abundance throughout the world (141–98 million years ago), but disappeared from the western North American fossil record (24–7 million years ago) (Del Tredici in Ginkgo biloba. Harwood Academic Publishers, Australia, 2000). Today, it is native only to China, with an annual production of 14,000 tons of ginkgo nut and 20,000 tons of ginkgo leaf primarily from Jiangsu, Shandong, Zhejiang, Hubei, Anhui and Guangxi provinces (Chen et al in Biomass Chem Eng 42:57–62, 2008).

The common sea-buckthorn ( Linnaeus, also known as Elaeagnus rhamnoides (Linnaeus) A. Nelson, or Moench) is a species of flowering plants of the family Elaeagnaceae, native to the dry temperate and cold desert areas of China, Russia, Mongolia, India, Pakistan, Nepal, Europe and North America. Comprising of eight subspecies, sea buckthorn is by far the most widespread species of the genus (Wu in Flora of China. Science Press and Missouri Botanical Garden Press, Beijing, 2007). The most common subspecies are H. rhamnoides (found in coastal North Europe), H. rhamnoides L. subsp. sinensis Rousi, H. rhamnoides L. subsp. gyantsensis Rousi, H. rhamnoides L. subsp. tibetana (Schlechtendal) Servettaz (found in China), and H. rhamnoides L. subsp. turkestanica Rousi (found in India, Afghanistan, Kazakhstan, Kyrgyzstan, Mongolia, Pakistan, Tajikistan, Turkmenistan and Uzbekistan).

A method has been established and validated for identification and quantification of individual, as well as total, anthocyanins by HPLC and LC/ES-MS in botanical raw materials used in the herbal supplement industry. The anthocyanins were separated and identified on the basis of their respective M(+) (cation) using LC/ES-MS. Separated anthocyanins were individually calculated against one commercially available anthocyanin external standard (cyanidin-3-glucoside chloride) and expressed as its equivalents. Amounts of each anthocyanin calculated as external standard equivalent were then multiplied by a molecular-weight correction factor to afford their specific quantities. Experimental procedures and use of a molecular-weight correction factors are substantiated and validated using Balaton tart cherry and elderberry as templates. Cyanidin-3-glucoside chloride has been widely used in the botanical industry to calculate total anthocyanins. In our studies on tart cherry and elderberry, its use as external standard followed by use of molecular-weight correction factors should provide relatively accurate results for total anthocyanins, because of the presence of cyanidin as their major anthocyanidin backbone. The method proposed here is simple and has a direct sample preparation procedure without any solid-phase extraction. It enables selection and use of commercially available anthocyanins as external standards for quantification of specific anthocyanins in the sample matrix irrespective of their commercial availability as analytical standards. It can be used as a template and applied for similar quantification in several anthocyanin-containing raw materials for routine quality control procedures, thus providing consistency in analytical testing of botanical raw materials used for manufacturing efficacious and true-to-the-label nutritional supplements.