miRNA Predictors of Pancreatic Cancer Chemotherapeutic Response: A Systematic Review and Meta-Analysis.

BACKGROUND: pancreatic cancer (PC) has increasing incidence and mortality in developing countries, and drug resistance is a significant hindrance to the efficacy of successful treatment. The objective of this systematic review and meta-analysis was to evaluate the association between miRNAs and response to chemotherapy in pancreatic cancer patients. METHODS: the systematic review and meta-analysis was based on articles collected from a thorough search of PubMed and Science Direct databases for publications spanning from January 2008 to December 2018. The articles were screened via a set of inclusion and exclusion criteria based on the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Data was extracted, collated and tabulated in MS Excel for further synthesis. Hazard ratio (HR) was selected as the effect size metric to be pooled across studies for the meta-analysis, with the random effects model being applied. Subgroup analysis was also conducted, and the presence of publication bias in the selected studies was assessed. Publication bias of the included studies was quantified. FINDINGS: of the 169 articles screened, 43 studies were included in our systematic review and 13 articles were included in the meta-analysis. Gemcitabine was observed to be the principal drug used in a majority of the studies. A total of 48 miRNAs have been studied, and 18 were observed to have possible contributions to chemoresistance, while 15 were observed to have possible contributions to chemosensitivity. 41 drug-related genetic pathways have been identified, through which the highlighted miRNA may be affecting chemosensitivity/resistance. The pooled HR value for overall survival was 1.603; (95% Confidence Interval (CI) 1.2-2.143; p-value: 0.01), with the subgroup analysis for miR-21 showing HR for resistance of 2.061; 95% CI 1.195-3.556; p-value: 0.09. INTERPRETATION: our results highlight multiple miRNAs that have possible associations with modulation of chemotherapy response in pancreatic cancer patients. Further studies are needed to discover the molecular mechanisms underlying these associations before they can be suggested for use as biomarkers of response to chemotherapeutic interventions in pancreatic cancer.

Investigation of anti-inflammatory and toxicity effects of mangrove-derived Streptomyces rochei strain VITGAP173.

Mangrove ecosystems generate the major biodiversity hotspots of actinobacteria. Among the actinobacteria, Streptomyces species are the prolific producers of bioactive natural products. In this study, with research efforts to discover biopotential compounds from marine actinobacteria, 41 actinobacterial strains were isolated from sediment soil sample of Indian mangrove regions. The phylogeny prediction using the 16S rRNA gene sequences revealed that the isolates were related to Streptomyces. Isolates were further screened based on a two-step process wherein the first step, around nine strains, unveiled the presence of type 1 polyketide synthase gene and dTDP-glucose 4,6-dehydratase gene through polymerase chain reaction. As the second step of the screening process, cell viability assay was performed in RAW264.7 cells to assess the toxicity of extracts. Among all the isolates, Streptomyces rochei strain VITGAP173 was subjected to further analysis. To explore the bioactivities, the organic solvent extraction method was utilized to extract the broth culture of VITGAP173. Inhibition of nitric oxide and cyclooxygenase enzymes upon lipopolysaccharide-induced inflammation were utilized to evaluate the anti-inflammatory efficacy, and the results showed the potency of VITGAP173 in a dose-dependent manner. The extract significantly suppressed the messenger RNA levels of the inflammatory mediators such as tumor necrosis factor-α and interleukin-6 induced by lipopolysaccharide in RAW264.7 macrophages. The presence of several chemical constituents was identified through gas chromatography-mass spectrometry analysis of VITGAP173 extract. To achieve the toxicity analysis, oral administration of VITGAP173 extract in Wistar albino rats was carried out to investigate the biochemical parameters, histopathology which revealed its nontoxic nature.

Bicarbonate supplementation enhances growth and biochemical composition of Dunaliella salina V-101 by reducing oxidative stress induced during macronutrient deficit conditions.

The unicellular marine alga Dunaliella salina is a most interesting green cell factory for the production of carotenes and lipids under extreme environment conditions. However, the culture conditions and their productivity are the major challenges faced by researchers which still need to be addressed. In this study, we investigated the effect of bicarbonate amendment on biomass, photosynthetic activity, biochemical constituents, nutrient uptake and antioxidant response of D. salina during macronutrient deficit conditions (N-, P- and S-). Under nutrient deficit conditions, addition of sodium bicarbonate (100 mM) significantly increased the biomass, carotenoids including ß-carotene and lutein, lipid, and fatty acid content with concurrent enhancement of the activities of nutrient assimilatory and carbonic anhydrase enzymes. Maximum accumulation of carotenoid especially ß-carotene (192.8 ± 2.11 µg/100 mg) and lipids (53.9%) was observed on addition of bicarbonate during nitrate deficiency compared to phosphate and sulphate deficiency. Supplementation of bicarbonate reduced the oxidative stress caused by ROS, lowered lipid peroxidation damage and improved the activities of antioxidant enzymes (SOD, CAT and APX) in D. salina cultures under nutrient stress.

Synergistic Action of D-Glucose and Acetosyringone on Agrobacterium Strains for Efficient Dunaliella Transformation.

An effective transformation protocol for Dunaliella, a ß-carotene producer, was developed using the synergistic mechanism of D-glucose and Acetosyringone on three different Agrobacterium strains (EHA105, GV3101 and LBA4404). In the present study, we investigated the pre-induction of Agrobacterium strains harboring pMDC45 binary vector in TAP media at varying concentrations of D-glucose (5 mM, 10 mM, and 15mM) and 100 µM of Acetosyringone for co-cultivation. Induction of Agrobacterium strains with 10 mM D-glucose and 100 µM Acetosyringone showed higher rates of efficiency compared to other treatments. The presence of GFP and HPT transgenes as a measure of transformation efficiency from the transgenic lines were determined using fluorescent microscopy, PCR, and southern blot analyzes. Highest transformation rate was obtained with the Agrobacterium strain LBA4404 (181 ± 3.78 cfu per 106 cells) followed by GV3101 (128 ± 5.29 cfu per 106 cells) and EHA105 (61 ± 5.03 cfu per 106 cells). However, the Agrobacterium strain GV3101 exhibited more efficient single copy transgene (HPT) transfer into the genome of D. salina than LBA4404. Therefore, future studies dealing with genetic modifications in D. salina can utilize GV3101 as an optimal Agrobacterium strain for gene transfer.

Effect of dissolved inorganic carbon on ß-carotene and fatty acid production in Dunaliella sp.

This study aimed to explore the effect of sodium bicarbonate (0-200 mM) on the production of ß-carotene and lipid content in Dunaliella salina and Dunaliella bardawil. Total carotenoid and chlorophyll content were determined at regular intervals by a UV-VIS spectrophotometer. The ß-carotene and lipid contents were analyzed using high-performance liquid chromatography (HPLC) and gas chromatography coupled with mass spectrometry (GC-MS). The HPLC results revealed a twofold increase of ß-carotene in D. salina and D. bardawil cultures grown with sodium bicarbonate. Moreover, total fatty acid profiles from GC-MS indicated a maximum relative percentage of saturated fatty acids (tetradecanoic acid, 10,13-diethyl, methyl ester and methyl 16-methyl-heptadecanoate) compared to polyunsaturated fatty acids in both algae. Our results indicate that the optimum concentration of bicarbonate (100 to 150 mM) was required to stimulate a positive effect on ß-carotene production as well as the lipid profile in Dunaliella sp.

OsPRP3, a flower specific proline-rich protein of rice, determines extracellular matrix structure of floral organs and its overexpression confers cold-tolerance.

Proline-rich protein (PRP), a cell wall protein of plant, has been studied in many plant species. Yet, none of the PRPs has been functionally elucidated. Here we report a novel flower-specific PRP designated OsPRP3 from rice. Expression analysis showed that the OsPRP3 transcript was mainly present in rice flower and accumulated abundantly during the late stage of the flower development. To study the function of OsPRP3, we constructed and transformed a binary vector containing a full clone of OsPRP3 in sense orientation and also an RNAi vector to achieve overexpression and knockout of the gene, respectively. Our overexpression plants showed a significant increase in cold tolerance than the WT plants which is conferred by the accumulation of OsPRP3 protein during cold treatment. Further the microscopic analysis revealed that OsPRP3 enhances the cell wall integrity in the cold tolerant plant and confers cold-tolerance in rice. Microscopic analysis of the RNAi mutant flower revealed that blocking OsPRP3 function caused significant defects in floral organogenesis. Taken together, the results suggested that OsPRP3 is a cell wall protein, playing a crucial role in determining extracellular matrix structure of floral organs.