Let-7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin-like growth factor 1 receptor

Abnormal expression of various microRNAs (miRNAs), as regulators of biological signaling pathways, has a strong association with cancer resistance to chemotherapy and radiotherapy. The let-7 family of miRNAs as tumor suppressors have shown to be downregulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let-7 members in the processes of resistance to radiation in CRC has not yet been completely elucidated. Insulin-like growth factor 1 receptor (IGF-1R) signaling pathway is amplified in CRC and leads to its progression, development, and also radiation resistance. So, it seems like an attractive target for anticancer therapy. In this study, by using bioinformatics analysis, it has been revealed that IGF-1R is a direct target of the let-7e member. Consistent with this, we identified that increased levels of let-7e in CRC cells reduced IGF-1R protein level and subsequently its downstream signaling pathways, which resulted in the G1 cell cycle arrest and a significant reduction in the proliferation, survival and also resistance to radiation of CRC cells. Altogether, these results suggested that let-7e by targeting the IGF-1R signaling pathway might serve as therapeutics in anticancer therapy.     

Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular-targeted therapies, targeted radionuclide therapies and epigenetic modification-based therapies. These topics are trending headlines and their combination with cell-based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.     

Centaurea shahuensis and C. ravansarensis spp. nov. (Asteraceae,Cardueae) from west Iran

Two new species of Centaurea L. sect. Cynaroides Boiss. ex Walp. (Asteraceae), C. shahuensis Ranjbar and Negaresh and C. ravansarensis Ranjbar and Negaresh are described and illustrated from Kermanshah Province, west Iran. They are closely related to C. regia Boiss. subsp. regia. However, C. shahuensis differs from it by median stem leaves broadly oblanceolate or subpandurate, phyllaries densely lanate‐tomentose, appendages small, concealing a minor part of phyllaries, and also median appendage margin entire sometimes with 1–2 cilia, 1.2–3.0 mm long on each side. Centaurea ravansarensis is distinguished by upper stem leaves loosely arachnoid, phyllaries loosely floccose‐tomentose, inner appendages deep brown to blackish, and spine 4.5–6.0 mm long. Habitat, conservation status and the geographical distribution of the new species are given.     

Optimization of the Emerson–Trinder enzymatic reaction by response surface methodology

The Emerson–Trinder reaction has been optimized in this work using an initial rate spectrophotometric method and response surface methodology (RSM). In this investigation, the variation range of critical variables along with the fixed parameters were selected based on a preliminary ‘one at a time’ (OVAT) procedure for the subsequent RSM chemometric analysis as follows: pH (6–10), buffer concentration (50–250?mM), 4-aminoantipyrine (4-AAP) concentration (1–5?mM), temperature (25–45°C). The optimum values of fixed parameters were: 4-fluorophenol (4-FP, 30?mM), horseradish peroxidase (HRP) enzyme activity (0.12?U?mL^?1), and the fixed concentration of the H₂O₂ in the chemometric experiments was 11.4 µM. The non-linear nature of the experimental response of the reaction system was explained by a second-order polynomial equation, which revealed the impact of the experimental factors, their interactions and also their optimum values. The results of the reported RSM analysis proved to be quite appropriate for the design and optimization of this reaction, as illustrated by the relatively high value of the determination coefficient (R²=96.7%) for the fitting of quadratic model, along with the satisfactory results generated by the analysis of variance (ANOVA). All the evaluated analytical characteristics of this method: typical reaction progress curves, resulting linear calibration curve, within-day precisions at low and at high levels, and the upper and lower detection limits were, also, reported. In addition, to check the quality of the optimization and validity of the model, the assay of H₂O₂, in pooled serum matrix and in cosmetic samples, was performed.     

Efficient clustering in collaborative filtering recommender system: Hybrid method based on genetic algorithm and gravitational emulation local search algorithm

The ultimate goal of the Recommender System (RS) is to offer a proposal that is very close to the user's real opinion. Data clustering can be effective in increasing the accuracy of production proposals by the RS. In this paper, single-objective hybrid evolutionary approach is proposed for clustering items in the offline collaborative filtering RS. This method, after generating a population of randomized solutions, at each iteration, improves the population of solutions first by Genetic Algorithm (GA) and then by using the Gravitational Emulation Local Search (GELS) algorithm. Simulation results on standard datasets indicate that although the proposed hybrid meta-heuristic algorithm requires a relatively high run time, it can lead to more appropriate clustering of existing data and thus improvement of the Mean Absolute Error (MAE), Root Mean Square Error (RMSE) and Coverage criteria.     

ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients

Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects.     

A taxonomic note on the Cephalaria sect. Atrocephalae (Caprifoliaceae) from Iran

Cephalaria kleinii Ranjbar & Z. Ranjbar sp. nova from Iran is described and illustrated. It is confined to Mazandaran province in northern Iran. The new species is closely related to C. kotschyi Boiss. & Hohen., but differs from it by its abaxial leaves colour, its basal leaves shape, dissection and petiole length, by the shape of apices of lateral and terminal segments of the cauline leaves, by the shape of apices of lateral and terminal segments of the upper leaves and by peduncle length. Furthermore, C. axillaris is resurrected and lectotypes are designated for C. axillaris and C. kotschyi for the first time.     

Heavy metals in the Rosetta estuary of the Nile and the adjoining Mediterranean waters: evidence of removal of dissolved heavy metals from waters as a result of possible binding to suspended matter

The Rosetta estuary was partially separated from the Rosetta branch of the Nile by Edfina Barrage, which controls the Nile discharge into the Mediterranean Sea. The study area covers the Rosetta estuary (lotic environment) and the adjoining seawaters (lentic environment) to investigate the local and seasonal distribution of dissolved and particulate copper and zinc, as well as dissolved cadmium in this estuary and to illustrate its influence on the distribution of these metal forms in the inshore seawaters. Besides, emphasis on the removal of dissolved heavy metals from waters by their adsorption onto suspended matter (SM) was also considered. Contrary to particulate copper (PCu), the vertical values of dissolved copper (DCu) decreased generally with depth. Planktonic scavenging and regeneration processes might determine the vertical profiles of the copper forms. The copper data suggest that the surface sources of DCu exceeded the bottom sources, contrary to the sources of PCu. The markedly high and maximum seasonal averages of DCu in the estuary and inshore seawater in July inspite of the high uptake in summer possibly reflect higher amounts of humic materials. The lowest seasonal average value of DCu in the inshore seawater in January suggests removal of copper in presence of maximum value of SM during highest discharge. The highest regional average of DCu at the estuarine mouth coincided with desorption process during mixing of the fresh and salt waters. The vertical values of dissolved zinc (DZn) and particulate zinc (PZn) showed irregular variations and their high concentrations in the surface of the estuarine and inshore seawater indicate possible land-based sources. The high bottom DZn values, however, resulted from its contribution from the interstitial water of the sediments. The data suggest that the surface sources of DZn exceeded the bottom sources and PZn showed the opposite trend in the open sea area. In the estuary, the maximum seasonal average value of DZn accompanied by the lowest seasonal average of PZn in April inspite of the high uptake in spring suggest that desorption was the dominant process. The minimum regional averages of both zinc forms at the estuarine opening and the highest average of PZn near Edfina Barage are correlated with the amounts of SM, which decreased toward the estuarine mouth. The vertical values of dissolved cadmium (DCd) were much lower in the estuary than the other metals. They showed in both environments irregular variations with depth. The bottom maximum value of DCd can be attributed mainly to contamination from the sediments. There was a distinct seasonal variation of DCd. The minimum seasonal average value of DCd in the estuary in April seems to be caused by its specific binding to living plankton found in abundance. The minimum regional average of DCd value was found at the estuarine mouth. The decrease in Cd concentration due to removal from dissolved state is most pronounced in the early stage of mixing. The correlation coefficients of DCd were positive with salinity and negative with SM, indicating that Cd increased seaward. Statistical correlation between Cd and Zn concludes that the factors affecting their distribution are generally the same.     

A newly identified c.1824_1828dupATACG mutation in exon 13 of the GAA gene in infantile-onset glycogen storage disease type II (Pompe disease)

Pompe disease or glycogen storage disease type II is a glycogen storage disorder associated with malfunction of the acid α-glucosidase enzyme (GAA; EC.3.2.1.3) leading to intracellular aggregations of glycogenin muscles. The infantile-onset type is the most life-threatening form of this disease, in which most of patients suffer from cardiomyopathy and hypotonia in early infancy. In this study, a typical case of Pompe disease was reported in an Iranian patient using molecular analysis of the GAA gene. Our results revealed a new c.1824_1828dupATACG mutation in exon 13 of the GAA gene. In conclusion, with the finding of this novel mutation, the genotypic spectrum of Iranian patients with Pompe disease has been extended, facilitating the definition of disease-related mutations.     

Differentiation of human embryonic stem cells to hepatocyte-like cells on a new developed xeno-free extracellular matrix

Human embryonic stem cells (hESCs) provide a new source for hepatocyte production in translational medicine and cell replacement therapy. The reported hESC-derived hepatocyte-like cells (HLCs) were commonly generated on Matrigel, a mouse cell line-derived extracellular matrix (ECM). Here, we performed the hepatic lineage differentiation of hESCs following a stepwise application of growth factors on a newly developed serum- and xeno-free, simple and cost-benefit ECM, designated “RoGel,” which generated from a modified conditioned medium of human fibroblasts. In comparison with Matrigel, the differentiated HLCs on both ECMs expressed similar levels of hepatocyte-specific genes, secreted α-fetoprotein, and metabolized ammonia, showed glycogen storage activity as well as low-density lipoprotein and indocyanine green uptake. The transplantation of hESC–HLCs into the carbon tetrachloride-injured liver demonstrated incorporation of the cells into the host mouse liver and the expression of albumin. The results suggest that the xeno-free and cost-benefit matrix may be applicable in bioartificial livers and also may facilitating a clinical application of human pluripotent stem cell-derived hepatocytes in the future.