Novel water-soluble polyurethane nanomicelles for cancer chemotherapy: physicochemical characterization and cellular activities

Background  

Efficient delivery of anticancer chemotherapies such as paclitaxel (PTX) can improve treatment strategy in a variety of tumors such as breast and ovarian cancers. Accordingly, researches on polymeric nanomicelles continue to find suitable delivery systems. However, due to biocompatibility concerns, a few micellar nanoformulations have exquisitely been translated into clinical uses. Here, we report the synthesis of novel water-soluble nanomicelles using bioactive polyurethane (PU) polymer and efficient delivery of PTX in the human breast cancer MCF-7 cells.     

Distribution of pathogenicity island markers and virulence factors in new phylogenetic groups of uropathogenic <Emphasis Type="Italic">Escherichia coli</Emphasis> isolates

The present study was aimed at investigating the relationship between the new Clermont’s phylogenetic groups, virulence factors, and pathogenicity island markers (PAIs) among uropathogenic Escherichia coli (UPEC) in Iran. This cross-sectional study was carried out on 140 UPEC isolates collected from patients with urinary tract infections in Bushehr, Iran. All isolates were subjected to phylogenetic typing using a new quadruplex-PCR method. The presence of PAI markers and virulence factors in UPEC strains was evaluated by multiplex PCR. The most predominant virulence gene was fimH (85%), followed by iucC (61.4%), papC (38.6%), hlyA (22.1%), cnf-1 (18.6%), afa (10.7%), papG and neuC (each 9.3%), ibeA (3.6%), and sfa/foc (0.7%). The most common phylogenetic group was related to B2 (39.3%), and the least common to A (0.7%). The most prevalent PAI marker was PAI IV536 (77.14%), while markers for PAI III536 (13.57%), PAI IIJ96 (12.86%), and PAI II536 (12.14%) were the least frequent among the UPEC strains. Meanwhile, the PAI IJ96 marker was not detected. There was a significant association between the phylogenetic group B2 and all the studied virulence genes and PAI markers. To our knowledge, this is the first study to compare the relationship between new phylogenetic groups, virulence genes and PAI markers in UPEC strains in Iran. The phylogenetic group B2 was predominantly represented among the studied virulence genes and PAI markers, indicating the preference of particular strains to carry virulence genes.     

Molecular characterization of acquired tolerance of tumor cells to picropodophyllin (PPP)

Background

Picropodophyllin (PPP) is a promising novel anti-neoplastic agent that efficiently kills tumor cells in vitro and causes tumor regression and increased survival in vivo. We have previously reported that PPP treatment induced moderate tolerance in two out of 10 cell lines only, and here report the acquired genomic and expression alterations associated with PPP selection over 1.5 years of treatment.

Methodology/Principal Findings

Copy number alterations monitored using metaphase and array-based comparative genomic hybridization analyses revealed largely overlapping alterations in parental and maximally tolerant cells. Gain/ amplification of the MYC and PVT1 loci in 8q24.21 were verified on the chromosome level. Abnormalities observed in connection to PPP treatment included regular gains and losses, as well as homozygous losses in 10q24.1-q24.2 and 12p12.3-p13.2 in one of the lines and amplification at 5q11.2 in the other. Abnormalities observed in both tolerant derivatives include amplification/gain of 5q11.2, gain of 11q12.1-q14.3 and gain of 13q33.3-qter. Using Nexus software analysis we combined the array-CGH data with data from gene expression profilings and identified genes that were altered in both inputs. A subset of genes identified as downregulated (ALDH1A3, ANXA1, TLR4 and RAB5A) or upregulated (COX6A1, NFIX, ME1, MAPK and TAP2) were validated by siRNA in the tolerant or parental cells to alter sensitivity to PPP and confirmed to alter sensitivity to PPP in further cell lines.

Conclusions

Long-term PPP selection lead to altered gene expression in PPP tolerant cells with increase as well as decrease of genes involved in cell death such as PTEN and BCL2. In addition, acquired genomic copy number alterations were observed that were often reflected by altered mRNA expression levels for genes in the same regions.     

Tumor microenvironment: Interactions and therapy

Tumor microenvironment (TME) is a host for a complex network of heterogeneous stromal cells with overlapping or opposing functions depending on the dominant signals within this milieu. Reciprocal paracrine interactions between cancer cells with cells within the tumor stroma often reshape the TME in favor of the promotion of tumor. These complex interactions require more sophisticated approaches for cancer therapy, and, therefore, advancing knowledge about dominant drivers of cancer within the TME is critical for designing therapeutic schemes. This review will provide knowledge about TME architecture, multiple signaling, and cross communications between cells within this milieu, and its targeting for immunotherapy of cancer.     

Definition of the affinity of binding between human von Willebrand factor and coagulation factor VIII

Factor VIII and von Willebrand factor are two plasma proteins essential for effective hemostasis. In vivo, they form a non-covalent complex whose association appears to be metal ion dependent. However, a precise definition of the nature of the molecular forces governing their association remains to be defined, as does their binding affinity. In this paper we have determined the dissociation constant and stoichiometry for Factor VIII binding to immobilized von Willebrand factor. The data demonstrate that these proteins interact saturably and with relatively high affinity. Computer assisted analyses of the Scatchard data favour a two site binding model. The higher affinity site was found to have a Kd of 62 (+/- 13) x 10(-12) M while that of the lower affinity site was 380 (+/- 92) x 10(-12) M. The density of Factor VIII binding sites (Bmax) present on von Willebrand factor was 31 (+/- 3) pM for the high affinity binding site and 46 (+/- 6) pM for the lower site, corresponding to a calculated Factor VIII: von Willebrand factor binding ratio of 1:33 and 1:23, respectively.     

Length‐weight and length‐length relationships of Oxynoemacheilus frenatus (Heckel, 1843) and Petroleuciscus esfahani Coad & Bogutskaya, 2010 from the Cheshmeh‐Langan river,Iran

The study presents length‐weight relationships (LWRs) and length‐lenght relationships (LLRs) for two freshwater fish species from the Cheshmeh‐Langan River (Iran; 32°50′N, 50°04′E), a part of the Tigris drainage basin. Fish were sampled by electrofishing (Samus 725M) in August and September 2017. The LWRs and LLRs obtained showed a high level of correlation (r² > .98).     

GENOMIC RELATIONSHIP OF GUAYULE WITH PARTHENIUM SCHOTTII

F₁ hybrids obtained from crosses between the rubber-bearing species, Parthenium argentatum Gray (commonly known as guayule), and P. schottii Greenman ex Millspaugh and Chase, a nonrubber-producing species from southern Mexico, were morphologically variable. They were generally intermediate between the two species with respect to leaf size, head size, number of disk florets per head, and the length of the peduncles. Like the parental species, the hybrids had 2n = 36 chromosomes. They averaged 14.56 bivalents, 3.92 univalents, 0.56 trivalents, and 0.32 quadrivalents, indicating a high degree of homeology between the genomes of the two species. The observation of one quadrivalent at diakinesis in 32% of the PMCs and the frequent occurrence of a bridge accompanied by a fragment at late anaphase I of the F, hybrids suggested that the two species differ in a reciprocal translocation and a paracentric inversion. The ease of hybridization, the partial fertility of the hybrids, and their high degree of chromosome pairing indicate that P. schottii and P. argentatum are closely related in spite of their distinct morphological features and geographical distributions. This close relationship provides an opportunity to transfer genes from P. schottii to guayule for desirable characteristics, such as high biomass production and resistance to Verticillium dahliae Kleb, by means of interspecific hybridization.     

Length–weight and length–length relationships for three Sillago species (Sillaginidae) from the Persian Gulf

This study investigates length–length and length–weight relationships of three Sillago species [Sillago arabica McKay & McCarthy (Memoirs of the Queensland Museum, 27, 1989, 551), Sillago attenuata McKay, 1985 and Sillago sihama (Forsskål, 1775)] captured in the Persian Gulf, Iran. A collection of 220 specimens was captured from August 2015 to January 2016 by cast net (mesh size: 10 mm) and beach seine (mesh size: 15 mm). The relationships of total length (TL) and standard length (SL) and the relationships between total length and body weight are given. This study presents the first reference on LWRs for two of the species (S. arabica and S. attenuata) in their range of distribution.     

Length–weight relationships of five commercial fish species from the Strait of Hormuz in the Persian Gulf

Length‐weight relationships are described for five fish species from the coast of the Hormuz Strait in the Persian Gulf, Iran. Specimens were collected between August 2010 and July 2011 using shrimp beam trawls, gill nets and intertidal fishing weirs. Relationships for three of the species had no previous data in the international science global databank on fishes: www.FishBase.org . A new maximum length was recorded for Acanthopagrus latus.