Effect of retinyl acetate on transglutaminase 2 activity in carcinogen treated rat liver

Transglutaminase 2 (TG2) has been implicated in wound healing, cellular differentiation, apoptosis and cell survival. TG2 activity increases following acute and chronic liver injury; however, the role of TG2 in tumors, is controversial. TG2 is a retinoid-inducible enzyme. We investigated the effects of retinyl acetate (RA) on the activity and levels of TG2 during the initiation and promotion stages of liver cancer. p-Dimethylaminoazobenzene (p-DAB) was used as initiator and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) was used as promoter in our model of carcinogenesis. Rats were divided into four groups of 24: control, corn oil control, p-DAB + TCDD, and p-DAB + TCDD + RA. Six rats from each group were sacrificed at days 30, 60, 90 and 120. TG2 activity decreased in the p-DAB + TCDD treated group, but TG2 immunostaining scores did not change by days 90 and 120. Neither TG2 enzyme activity nor the immunostaining score of TG2 protein changed in the tissues of the p-DAB + TCDD + RA group by days 90 and 120. TG2 activity was not be ameliorated by RA during the initiation or promotion stages of carcinogen induced liver cancer.     

In vitro expression of secondary antitumor immunity by in vivo tumor-sensitized T cells: Inhibition by tumor-induced suppressor T cells

Summary In vitro cultivation of memory immune cells from P815- or P388-immune mice with corresponding irradiated tumor cells induced generation of cytolytic T cells (CTL). The induction of CTL generation, as well as the cytolytic activity itself, was tumor-specific. The in vitro generation of CTL from P815- or P388-immune cells was suppressed by spleen cells from mice bearing corresponding progressive tumors (tumor size 15 mm). The tumor-induced suppressor cells suppressed the in vitro generation of CTL, but did not affect their cytolytic function. The suppression was tumor-specific and was mediated by Ly1⁺2^–L3T4⁺ T cells. Treatment of suppressor cell donors with cyclophosphamide or sublethal -radiation completely abolished the ability of their spleen cells to inhibit the in vitro CTL generation.     

Silencing of the MEG3 gene promoted anti-cancer activity and drug sensitivity in glioma

Aberrant expression of MEG3 has been shown in various cancers. The purpose of this study is to evaluate the effect of MEG3 on glioma cells and the use of potential chemotherapeutics in glioma by modulating MEG3 expression. Cell viability, migration and chemosensitivity were assayed. Cell death was evaluated in MEG3 overexpressing and MEG3 suppressed cells. MEG3 expression was compared in patient-derived glioma cells concerning IDH1 mutation and WHO grades. Silencing of MEG3 inhibited cell proliferation and reduced cell migration while overexpression of MEG3 promoted proliferation in glioma cells. MEG3 inhibition improved the chemosensitivity of glioma cells to 5-fluorouracil (5FU) but not to navitoclax. On the other hand, there is no significant effect of MEG3 expression on temozolamide (TMZ) treatment which is a standard chemotherapeutic agent in glioma. Suppression of the MEG3 gene in patient-derived oligodendroglioma cells also showed the same effect whereas glioblastoma cell proliferation and chemosensitivity were not affected by MEG3 inhibition. Further, as a possible cell death mechanism of action apoptosis was investigated. Although MEG3 is a widely known tumour suppressor gene and its loss is associated with several cancer types, here we reported that MEG3 inhibition can be used for improving the efficiency of known chemotherapeutic drug sensitivity. We propose that the level of MEG3 should be evaluated in the treatment of different glioma subtypes that are resistant to effective drugs to increase the potential effective drug applications.     

Effect of Axial Ligand Length on Biological and Anticancer Properties of Axially Disubstituted Silicon Phthalocyanines

In this study, three new axially disubstituted silicon phthalocyanines ( SiPc1–3 ) and their quaternized phthalocyanine derivatives ( QSiPc1–3 ) were prepared and characterized. The biological properties (antioxidant, antimicrobial, antibiofilm, and microbial cell viability activities) of the water-soluble silicon phthalocyanines were examined, as well. A 1 % DMSO diluted with pure water was used as a solvent in biological activity studies. All the compounds exhibited high antioxidant activity. They displayed efficient antimicrobial and antimicrobial photodynamic therapeutic properties against various microorganisms, especially Gram (+) bacteria. Additionally, they demonstrated high antibiofilm activities against S. aureus and P. aeruginosa. In addition, 100 % bacterial reduction was obtained for all the studied phthalocyanines against E. coli viable cells. Besides, the DNA cleavage and binding features of compounds ( QSiPc1–3 ) were studied using pBR322 DNA and CT-DNA, respectively. Furthermore, the human topoisomerase I enzyme inhibition activities of compounds QSiPc1 – 3 were studied. Anticancer properties of the water-soluble compounds were investigated using cell proliferation MTT assay. They exhibited anticarcinogenic activity against the human colon cancer cell line (DLD-1). Compounds QSiPc1 and QSiPc3 displayed a high anticarcinogenic effect on the DLD-1 cell line. The obtained results indicated that all the studied compounds may be effective biological agents and anticancer drugs after further investigations.     

Fluorinated Phthalocyanine/Silver Nanoconjugates for Multifunctional Biological Applications

In this study, a new phthalonitrile derivative namely 4-[(2,4-difluorophenyl)ethynyl]phthalonitrile ( 1 ) and its metal phthalocyanines ( 2 and 3 ) were synthesized. The resultant compounds were conjugated to silver nanoparticles and characterized using transmission electron microscopy (TEM) images. The biological properties of compounds ( 1 – 3 ), their nanoconjugates ( 4 – 6 ), and silver nanoparticles ( 7 ) were examined for the first time in this study. The antioxidant activities of biological candidates ( 1 – 7 ) were studied by applying the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The highest antioxidant activity was obtained 97.47 % for 200 mg/L manganese phthalocyanine-silver nanoconjugates ( 6 ). The antimicrobial and antimicrobial photodynamic therapy (APDT) activities of biological candidates ( 1 – 7 ) were examined using a micro-dilution assay. The highest MIC value was obtained 8 mg/L for nanoconjugate 6 against E. hirae. The studied compounds and their silver nanoconjugates exhibited high APDT activities against all the studied microorganisms. The most effective APDT activities were obtained 4 mg/L for nanoconjugates ( 5 and 6 ) against L. pneumophila and E. hirae, respectively. All the studied biological candidates displayed high cell viability inhibition activities against E. coli cell growth. The biofilm inhibition activities of the tested biological candidates were also investigated against S. aureus and P. Aeruginosa. Biological candidates ( 1 – 6 ) can be considered efficient metal nanoparticle-based materials for multi-disciplinary biological applications.     

Inositol‐requiring enzyme‐1 regulates phosphoinositide signaling lipids and macrophage growth

The ER‐bound kinase/endoribonuclease (RNase), inositol‐requiring enzyme‐1 (IRE1), regulates the phylogenetically most conserved arm of the unfolded protein response (UPR). However, the complex biology and pathology regulated by mammalian IRE1 cannot be fully explained by IRE1’s one known, specific RNA target, X box‐binding protein‐1 (XBP1) or the RNA substrates of IRE1‐dependent RNA degradation (RIDD) activity. Investigating other specific substrates of IRE1 kinase and RNase activities may illuminate how it performs these diverse functions in mammalian cells. We report that macrophage IRE1 plays an unprecedented role in regulating phosphatidylinositide‐derived signaling lipid metabolites and has profound impact on the downstream signaling mediated by the mammalian target of rapamycin (mTOR). This cross‐talk between UPR and mTOR pathways occurs through the unconventional maturation of microRNA (miR) 2137 by IRE1’s RNase activity. Furthermore, phosphatidylinositol (3,4,5) phosphate (PI(3,4,5)P₃) 5‐phosphatase‐2 (INPPL1) is a direct target of miR‐2137, which controls PI(3,4,5)P₃ levels in macrophages. The modulation of cellular PI(3,4,5)P₃/PIP₂ ratio and anabolic mTOR signaling by the IRE1‐induced miR‐2137 demonstrates how the ER can provide a critical input into cell growth decisions.     

Synthesis and Biological Activities of Nicotinaldehyde Based 1,4-Dihydropyridinedicarboxylates

Russian Journal of Bioorganic Chemistry - 1,4-Dihydropyridinecarboxylates were prepared by the reaction of nicotinaldehydes with aminocrotonoates in the presence of p-TsOH at room temperature. The...     

Population genetic structure of turbot (Scophthalmus maximus L., 1758) in the Black Sea

Turbot, Scophthalmus maximus, is a commercially important demersal flatfish species distributed throughout the Black Sea. Several studies performed locally with a limited number of specimens using both mitochondrial DNA (mtDNA) and microsatellite markers evidenced notable genetic variation among populations. However, comprehensive population genetic studies are required to help management of the species in the Black Sea. In the present study eight microsatellite loci were used to resolve the population structure of 414 turbot samples collected from 12 sites across the Black Sea. Moreover, two mtDNA genes, COI and Cyt-b, were used for taxonomic identification. Microsatellite markers of Smax-04 and B12-I GT14 were excluded from analysis due to scoring issues. Data analysis was performed with the remaining six loci. Loci were highly polymorphic (average of 17.8 alleles per locus), indicating high genetic variability. Locus 3/20CA17, with high null allele frequency (>30%), significantly deviated from HW equilibrium. Pairwise comparison of the F_ST index showed significant differences between most of the surveyed sampling sites (P < 0.01). Cluster analysis evidenced the presence of three genetic groups among sampling sites. Significant genetic differentiation between Northern (Sea of Azov and Crimea) and Southern (Turkish Black Sea Coast) Black Sea sampling sites were detected. The Mantel test supported an isolation by distance model of population structure. These findings are vital for long-term sustainable management of the species and development of conservation programs. Moreover, generated mtDNA sequences would be useful for the establishment of a database for S. maximus.     

Supplementation of Taurine Insulates Against Oxidative Stress,Confers Neuroprotection and Attenuates Memory Impairment in Noise Stress Exposed Male Wistar Rats

Noise has always been an important environmental factor that induces health problems in the general population. Due to ever increasing noise pollution, humans are facing multiple auditory and non-auditory problems including neuropsychiatric disorders. In modern day life it is impossible to avoid noise due to the rapid industrialization of society. Continuous exposure to noise stress creates a disturbance in brain function which may lead to memory disorder. Therefore, it is necessary to find preventive measures to reduce the deleterious effects of noise exposure. Supplementation of taurine, a semi essential amino acid, is reported to alleviate psychiatric disorders. In this study noise-exposed (100 db; 3 h daily for 15 days) rats were supplemented with taurine at a dose of 100 mg/kg for 15 days. Spatial and recognition memory was assessed using the Morris water maze and novel object recognition task, respectively. Results of this study showed a reversal of noise-induced memory impairment in rats. The derangements of catecholaminergic and serotonergic levels in the hippocampus and altered brain antioxidant enzyme activity due to noise exposure were also restored by taurine administration. This study highlights the importance of taurine supplementation to mitigate noise-induced impaired memory via normalizing the neurochemical functions and reducing oxidative stress in rat brain.

     

Biocontrol of wilt disease complex of pea using Pseudomonas fluorescens and Rhizobium sp.

Biocontrol of wilt disease complex of pea caused by the root-knot nematode Meloidogyne incognita and Fusarium oxysporum f. sp. pisi was studied on pea (Pisum sativum L.) using plant growth-promoting rhizobacterium Pseudomonas fluorescens and root nodule bacterium Rhizobium sp. Inoculation of M. incognita and F.oxysporum alone caused significant reductions in plant growth over un-inoculated control. Reduction in plant growth caused by M. incognita was statistically equal to that caused by F. oxysporum. Inoculation of M. incognita plus F. oxysporum together caused a greater reduction in plant growth than the sum of damage caused by these pathogens singly. Inoculation of P. fluorescens and Rhizobium sp. individually or both together increased plant growth in pathogen inoculated and un-inoculated plants. Inoculation of P. fluorescens to pathogen-inoculated plants caused a greater increase in plant growth than caused by Rhizobium sp. Application of Rhizobium plus P. fluorescens caused a greater increase in plant growth than caused by each of them singly. Inoculation of P.fluorescens caused higher reduction in galling and nematode multiplication than caused by Rhizobium sp. Use of Rhizobium plus P. fluorescens caused higher reduction in galling and nematode multiplication than their individual inoculation. Plants inoculated with both pathogens plus Rhizobium showed less nodulation than plants inoculated with single pathogen plus Rhizobium. Inoculation of Rhizobium plus P. fluorescens resulted in higher root-nodulation than inoculated only with Rhizobium. Wilting indices were 4 and 5, respectively, when plants were inoculated with F. oxysporum and F. oxysporum plus M. incognita. Wilting indices were reduced maximum to 1 and 2, respectively, when plants inoculated with F.oxysporum and plants with both pathogens were treated with P. fluorescens plus Rhizobium.