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In animal cells, mitochondria are the primary powerhouses and metabolic factories. They also contain genomes and can produce mitochondrial-specific nucleic acids and proteins. To maintain homeostasis of the entire cell, an intense cross-talk between mitochondria and the nucleus, mediated by encoded noncoding RNAs (ncRNAs), as well as proteins, is required. Long ncRNAs (lncRNAs) contain characteristic structures, and they are involved in the regulation of almost every stage of gene expression, as well as being implicated in a variety of disease states, such as cancer. In the coordinated signaling system, several lncRNAs, transcribed in the nucleus but residing in mitochondria, play a key role in regulating mitochondrial functions or dynamics. For example, RMRP, a component of the mitochondrial RNase MRP, is important for mitochondrial DNA replication and RNA processing, and the steroid receptor RNA activator, SRA, is a key modulator of hormone signaling and is present in both the nucleus and mitochondria. Some RNA-binding proteins maybe play a role in the lncRNAs transport system, such as HuR, GRSF1, SHARP, SLIRP, PPR, and PNPASE. Furthermore, a series of nuclear DNA-encoded lncRNAs were implicated in mitochondria-mediated apoptosis, mitochondrial bioenergetics and biosynthesis, and glutamine metabolism. The mitochondrial genome can also encode a set of lncRNAs, and they are divided into three categories: (1) lncND5, lncND6, and lncCyt b RNA; (2) chimeric mitochondrial DNA-encoded lncRNAs; and (3) putative mitochondrial DNA-encoded lncRNAs. It has been reported that the mitochondrial DNA-encoded lncRNAs appear to operate in the nucleus. The molecular mechanisms underlying trafficking of the mitochondrial DNA-encoded lncRNAs to the nucleus in mammals are only now beginning to emerge. In conclusion, both nuclear- and mitochondrial DNA-encoded lncRNAs mediate an intense intercompartmental cross-talk, which opens a rich field for investigation of the mechanism underlying the intercompartmental coordination and the maintenance of whole cell homeostasis.

Background Recent studies have focused on the significant cytotoxicity of natural killer (NK) cells, cytokine-induced killer (CIK) cells, and gamma-delta (γδ) T cells in tumor cells. Nevertheless, the therapeutic features of these cell types have not been compared in the literature. The aim of this study was to evaluate the feasibility of activation and expansion of NK, CIK, and γδ T cells from cancer patients in vitro, and to clarify the differences in their antitumor capacities. Methods NK, CIK, and γδ T cells were induced from the peripheral blood mononuclear cells of 20 cancer patients by using specific cytokines. Expression of CD69, NKG2D, CD16, granzyme B, perforin, IFN-γ, and IL-2 was measured by flow cytometry. Cytokine production and cytotoxicity were analyzed by enzyme-linked immunosorbent assay and Calcein-AM methods. Results NK cell proliferation was superior to that of CIK cells, but lower than that of γδ T cells. NK cells had a much stronger ability to secrete perforin, granzyme B, IFN-γ, and IL-2 than did CIK and γδ T cells, and imparted significantly higher overall cytotoxicity. Conclusions Expanded NK cells from cancer patients are the most effective immune cells in the context of cytokine secretion and anti-tumor cytotoxicity in comparison to CIK and γδ T cells, making them an optimal candidate for adoptive cellular immunotherapy.

1. DNA methylation is a critical epigenetic modification that silences gene transcription, participates in X-chromosome inactivation in females, and regulates genomic imprinting. 2. We have devised a method to inhibit transcriptional initiation by constructing short methylated oligonucleotides which induce DNA methylation at specific loci. 3. The methodology by which we devise these oligonucleotides is described, using oligonucleotides directed against the oncogene, Bcl-2.4. The human Bcl-2 gene contains two promoters, each of which contains a CpG island in its core region. Oligonucleotides are designed which can inhibit Bcl-2 transcription and lead to decreased mRNA and protein in vitro. When compared to standard anti-sense oligonucleotide action, these methylated oligonucleotides are far more sensitive and potentially, longer acting. 5. In principle, using this methodology, it should be possible to design methylated oligonucleotides that can methylate CpG islands and thereby downregulate any gene.

Using sodium silicate as precursor, rod-like mesoporous silica with hexagonal appearance was synthesized by controlling the pH value of a mixed micelles solution of cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC) during hydrolysis of ethyl acetate. The resulting mesoporous silica was characterized by small angle X-ray diffraction, nitrogen gas adsorption-desorption measurement and scanning electron microscopy. Results showed that the regular rod-like shapes with hexagonal appearance were obtained at a 9:1 molar ratio of CTAB to CTAC, and that the amounts and lengths of the rod-like mesoporous silica particles decreased with decreasing CTAB to CTAC molar ratio. There existed a type IV adsorption isotherm and an H1 hysteresis loop in N2 gas adsorption-desorption curves.

The zero point of charge (ZPC) and the intrinsic ionization constant ( % MathType!MTEF!2!1!+- % feaaeaart1ev0aaatCvAUfKttLearuavTnhis1MBaeXatLxBI9gBae % bbnrfifHhDYfgasaacH8srps0lbbf9q8WrFfeuY-Hhbbf9v8qqaqFr % 0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qqQ8 % frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeaadaaakeaacqWG % lbWsdaqhaaWcbaGaeeyyaegabaGaeeyAaKMaeeOBa4MaeeiDaqhaaa % aa!304C! $$ K_{\rm a}^{{\rm int}} $$ ) of Zn−Mg−Al hydrotalcite-like compounds (HTlc) with the general formula [(Zn,Mg)1− x Al x (OH)2] x + [(OH,Cl) x ] x − were determined by potentiometric titration (PT). The variation of the ZPC and % MathType!MTEF!2!1!+- % feaaeaart1ev0aaatCvAUfKttLearuavTnhis1MBaeXatLxBI9gBae % bbnrfifHhDYfgasaacH8srps0lbbf9q8WrFfeuY-Hhbbf9v8qqaqFr % 0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qqQ8 % frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeaadaaakeaacqWG % lbWsdaqhaaWcbaGaeeyyaegabaGaeeyAaKMaeeOBa4MaeeiDaqhaaa % aa!304C! $$ K_{\rm a}^{{\rm int}} $$ with x was investigated. For the colloidal particles possessing permanent charges, the ZPC determined by the PT method is the zero point of net charge (ZPNC). The ZPNC ( pH ZPNC) values were 9.63 {[Zn0.27Mg0.36Al0.37 (OH)2]Cl0.13 (OH)0.24 }, 9.68 {[Zn0.13 Mg0.58Al0.29 (OH)2]Cl0.12 (OH)0.17 }, 9.67 {[Zn0.17Mg0.54Al0.29 (OH)2]Cl0.16 (OH)0.12 },10.16 {[Zn0.08Mg0.67Al0.25 (OH)2]Cl0.17 (OH)0.08}, 10.33 {[Zn0.16 Mg0.60 Al0.24 (OH)2] Cl0.16 (OH)0.08} and 10.60 {[Zn 0.19Mg0.60 Al0.21 (OH)2] Cl0.15 (OH)0.06}; the intrinsic ionization constants % MathType!MTEF!2!1!+- % feaaeaart1ev0aaatCvAUfKttLearuavTnhis1MBaeXatLxBI9gBae % bbnrfifHhDYfgasaacH8srps0lbbf9q8WrFfeuY-Hhbbf9v8qqaqFr % 0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qqQ8 % frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeaadaaakeaacqqG % WbaCcqWGlbWsdaqhaaWcbaGaeeyyaeMaeeOmaidabaGaeeyAaKMaee % OBa4MaeeiDaqhaaaaa!329E! $$ {\rm p}K_{{\rm a2}}^{{\rm int}} $$ of the same HTlc samples were 10.31, 10.44, 10.44, 11.02, 11.19 and 11.54. With decreasing x, ZPNC and % MathType!MTEF!2!1!+- % feaaeaart1ev0aaatCvAUfKttLearuavTnhis1MBaeXatLxBI9gBae % bbnrfifHhDYfgasaacH8srps0lbbf9q8WrFfeuY-Hhbbf9v8qqaqFr % 0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qqQ8 % frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeaadaaakeaacqWG % lbWsdaqhaaWcbaGaeeyyaeMaeeOmaidabaGaeeyAaKMaeeOBa4Maee % iDaqhaaaaa!3137! $$ K_{{\rm a2}}^{{\rm int}} $$ of HTlc increased, and the acidity of the HTlc samples decreased.

Background Colorectal cancer is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality observed in human colorectal neoplasms. Our aim was to investigate the feasibility of using the IGF2 imprinting system for targeted gene therapy of colorectal cancer. Results We constructed a novel oncolytic adenovirus, Ad315-E1A, and a replication-deficient recombinant adenovirus, Ad315-EGFP, driven by the IGF2 imprinting system by inserting the H19 promoter, CCCTC binding factor, enhancer, human adenovirus early region 1A (E1A) and enhanced green fluorescent protein (EGFP) reporter gene into a pDC-315 shuttle plasmid. Cell lines with IGF2 LOI (HCT-8 and HT-29), which were infected with Ad315-EGFP, produced EGFP. However, no EGFP was produced in cell lines with maintenance of imprinting (HCT116 and GES-1). We found that Ad315-E1A significantly decreased cell viability and induced apoptosis only in LOI cell lines in vitro. In addition, mice bearing HCT-8-xenografted tumors, which received intratumoral administration of the oncolytic adenovirus, showed significantly reduced tumor growth and enhanced survival. Conclusions Our recombinant oncolytic virus targeting the IGF2 LOI system inhibits LOI cell growth in vitro and in vivo, and provides a novel approach for targeted gene therapy.