The potential roles of retinoids in combating drug resistance in cancer: implications of ATP-binding cassette (ABC) transporters

Multidrug resistance (MDR) means that tumour cells become unresponsive during or after the course of treatment to one or more of chemotherapeutic drugs. Chemotherapeutic resistance critically limits the treatment outcomes and remains a key challenge for clinicians. The alternation in intracellular drug concentration through the modulation of its transport across the plasma membrane is the major cause for MDR and is adopted by various mediators, including ATP-requiring enzymes (ATPases). Among these ATPases, ABC transporters have been extensively studied, and found to be highly implicated in tumorigenesis and MDR. The present review sheds light on the documented effects of retinoids on ABC enzymes to understand their mechanism in combating cancer cell resistance. This would open the gate to test the mechanism and applicability of different new synthetic retinoids in literature and market as modulators of ATP-dependent efflux pumping activity, and promote their applicability in diminishing anti-cancer drug resistance.     

Impacts of cell surface characteristics on population dynamics in a sequencing batch yeast reactor treating vegetable oil-containing wastewater

Ten yeast strains acquired from different sources and capable of utilizing vegetable oil or related compounds (fatty acid or oleic acid) as sole carbon sources were inoculated into a sequencing batch reactor (SBR) for the treatment of high-strength vegetable oil-containing wastewater. The SBR system stably removed >89% of chemical oxygen demand (COD) and >99% of oil when fed with wastewater containing 15 g/L COD and 10 g/L oil in average. Denaturing gradient gel electrophoresis of polymerase chain reaction-amplified 26S rRNA genes showed that among the ten yeast strains, only Candida lipolytica, Candida tropicalis, and Candida halophila were dominant in the system. To elucidate the major factors affecting the selection of yeast strains in the SBR system, the three dominant strains were compared with two non-dominant strains in terms of COD removal performance, biomass yield, cell settleability, cell flocculation ability, cell emulsification ability, and surface hydrophobicity. Results showed that hydrophobicity and emulsification ability of yeast cells were the two most important factors determining the selection of yeast strains in the treatment of high-strength oil-containing wastewater.     

Genetic assessment of the internal transcribed spacer region (ITS1.2) in Mangifera indica L. landraces

Mango (Mangifera indica) is one of the most important tropical fruits in the world. Twenty-two genotypes of native mangoes from different regions of southern Iran (Hormozgan and Kerman) were collected and analyzed for the ribosomal genes. GC content was found to be 55.5%. Fu and Li’s D* test statistic (0.437), Fu and Li’s F* test statistic (0.500) and Tajima’s D (1.801) were positive and nonsignificant. A total of 769 positions were identified (319 with insertion or deletion including 250 polymorphic and 69 monomorphic loci; 450 loci without any insertion or deletion including 35 Singletons and 22 haplotypes). Nucleotide diversity of 0.309 and a high genetic differentiation including Chi square of 79.8; P value of 0.3605 and df value of 76 was observed among mango genotypes studied. The numerical value of the ratio dN/dS (0.45) indicated a pure selection in the examined gene and the absence of any key changes. Cluster analysis differentiated the mango used in this research (M. indica L.) into two genotypes but could not differentiate their geographical locations. The results of this study indicated that a high genetic distance exists between HajiGholam (Manojan) and Arbabi (Rodan) genotypes and showed higher genetic diversity in mango of Rodan region. Results of present study suggested that for successful breeding, the genotypes of Rodan region mango especially Arbabi mango can be used as a gene donor and ITS can be a suitable tool for genetic evaluations of inter and intra species.     

Foliar Application of Phosphorus Enhances Photosynthesis and Biochemical Characteristics of Maize under Drought Stress

Water is essential for the growth period of crops; however, water unavailability badly affects the growth and physiological attributes of crops, which considerably reduced the yield and yield components in crops. Therefore, a pot experiment was conducted to investigate the effect of foliar phosphorus (P) on morphological, gas exchange, biochemical traits, and phosphorus use efficiency (PUE) of maize (Zea mays L.) hybrids grown under normal as well as water deficit situations at the Department of Agronomy, University of Agriculture Faisalabad, Pakistan in 2014. Two different treatments (control and P @ 8 kg ha⁻¹ ) and four hybrids (Hycorn, 31P41, 65625, and 32B33) of maize were tested by using a randomized complete block design (RCBD) with three replications. Results showed that the water stress caused a remarkable decline in total soluble protein (9.7%), photosynthetic rate (9.4%) and transpiration rate (13.4%), stomatal conductance (10.2%), and internal CO₂ rate (20.4%) comparative to well-watered control. An increase of 37.1%, 36.8%, and 24.5% were recorded for proline, total soluble sugar, and total free amino acid, respectively. However, foliar P application minimized the negative impact of drought by improving plant growth, physio-biochemical attributes, and PUE in maize plants under water stress conditions. Among the hybrids tested, the hybrid 6525 performed better both under stress and non-stress conditions. These outcomes confirmed that the exogenous application of P improved drought stress tolerance by modulating growth, physio-biochemical attributes, and PUE of maize hybrids.     

Evolutionary profile of the family Calliphoridae,with notes on the origin of myiasis

The family Calliphoridae is a group of heterogenous calyptrate flies with a worldwide distribution including species of ecological, veterinary, medical, and forensic importance. Notorious for their parasitic habits, the larvae of many blowflies are characterised – like some other dipteran larvae – by their ability to develop in animal flesh. When parasitism affects a living host, it is termed “myiasis”. This has led the Calliphoridae to be considered as a pivotal family in its relationship with a man. Nevertheless, even after more than 50 years of research, the phylogenetic relationships among calliphorid subfamilies together with the evolutionary origin of myiasis remain unclear. In order to elucidate these problems, we constructed three phylogenetic trees by using nucleotide sequence data from cytochrome oxidase subunit one (COI), representing a mitochondrial conservative gene, and nuclear 28S subunit of ribosomal RNA gene (28S rRNA) in order to interpret the evolutionary profile of myiasis in the family Calliphoridae. The sequenced data represented species associated with ectoparasitic life-styles, either saprophagy or facultative and obligate parasitism. A total number of 50 accessions were collected for 28S rRNA, 56 for COI, and 38 for combined sequences phylogeny. Molecular Evolutionary Genetics Analysis (MEGA) software was used to align 2197 nucleotide positions of 28S rRNA and 1500 nucleotide positions of COI with a gap opening penalties and gap extension penalties equalling 20 and 0.1 respectively. The results reveal the non-monophyly of the family Calliphoridae despite the stable monophyletic status of the Chrysomyinae, Luciliinae, and Auchmeromyiinae. Also, our findings recommend ranking the Toxotarsinae as a separate family. Furthermore, comparative analysis of the phylogenetic trees shows that the habit of obligatory myiasis originated independently more than five times. This strengthens our hypothesis that the origin of eating fresh meat is a case of convergent evolution that has taken place after speciation events millions of years ago. Finally, estimating the divergence dates between lineages from molecular sequences provides a better chance of understanding their evolutionary biology.     

Assessment of genetic diversity and phylogenetic relationship among grouper species Epinephelus spp. from the Saudi waters of the Arabian Gulf

Understanding of fish genetic characterization plays a vital role in the conservation and utilization of fish genetic resources of grouper species. The present study was carried out to assess the genetic diversity and phylogenetic relationships in five grouper species, Epinephelus spp. from eastern Saudi Arabian coast using two molecular marker systems, inter simple sequence repeat (ISSR) and microsatellite (SSR) markers. In total, 219 individuals grouper specimens (Epinephelus tauvina, E. coioides, E. bleekeri, E. malabaricus, and E. areolatus) were genotyped with 10 ISSR and 11 SSR selected primers. The ISSR produced 94 DNA fragments, of which 44 were polymorphic with an average of 2.13 fragment per primer. While SSR primers generated 107 alleles, all of them were polymorphic with an average 9.72 per primer. ISSR and SSR techniques demonstrated a high level of gene diversity and genetic distances illustrated by UPGMA dendrograms among the grouper species. The results proved that the SSR markers were highly informative and efficient in detecting genetic variability and relationships of the Epinephelus spp.     

Spectrofluorimetric determination of certain biologically active phenothiazines in commercial dosage forms and human plasma

A validated simple and sensitive spectrofluorimetric method was developed for the determination of chlorpromazine hydrochloride, promethazine hydrochloride, trifluperazine hydrochloride, thioridazine hydrochloride, perazine maleate and oxomemazine. The method was based on condensation of malonic acid/acetic anhydride (MAA) under the catalytic effect of the tertiary amine moiety of the studied phenothiazines to provide a deep yellow to brown colour with green florescence. Relative fluorescence intensity of the products was measured at λ_exc 398 nm and λ_em 432 nm. Different variables affecting the reaction were studied and optimized. The method was successfully applied for the determination of the studied drugs in commercial dosage forms. The lower detection limits allowed the application of this method for the determination of the compounds in plasma as an example of a biological fluid. In addition, the method was considered specific for the determination of tertiary amines in the presence of primary and secondary amines; as a result, it was deemed suitable for the determination of the cited drugs in the presence of their degradation products resulting from N‐dealkylation or oxidation of the corresponding sulphoxides or sulphones. Copyright © 2012 John Wiley & Sons, Ltd.     

Subtype Distribution of Blastocystis Isolates in Sebha,Libya

Background

Blastocystis is a genetically diverse and a common intestinal parasite of humans with a controversial pathogenic potential. This study was carried out to identify the Blastocystis subtypes and their association with demographic and socioeconomic factors among outpatients living in Sebha city, Libya.

Methods/Findings

Blastocystis in stool samples were cultured followed by isolation, PCR amplification of a partial SSU rDNA gene, cloning, and sequencing. The DNA sequences of isolated clones showed 98.3% to 100% identity with the reference Blastocystis isolates from the Genbank. Multiple sequence alignment showed polymorphism from one to seven base substitution and/or insertion/deletion in several groups of non-identical nucleotides clones. Phylogenetic analysis revealed three assemblage subtypes (ST) with ST1 as the most prevalent (51.1%) followed by ST2 (24.4%), ST3 (17.8%) and mixed infections of two concurrent subtypes (6.7%).

Blastocystis

ST1 infection was significantly associated with female (P = 0.009) and low educational level (P = 0.034). ST2 was also significantly associated with low educational level (P= 0.008) and ST3 with diarrhoea (P = 0.008).

Conclusion

Phylogenetic analysis of Libyan Blastocystis isolates identified three different subtypes; with ST1 being the predominant subtype and its infection was significantly associated with female gender and low educational level. More extensive studies are needed in order to relate each Blastocystis subtype with clinical symptoms and potential transmission sources in this community.     

Burden of Giardia duodenalis Infection and Its Adverse Effects on Growth of Schoolchildren in Rural Malaysia

Background

Giardia duodenalis infection and malnutrition are still considered as public health problems in many developing countries especially among children in rural communities. This study was carried out among Aboriginal (Orang Asli) primary schoolchildren in rural peninsular Malaysia to investigate the burden and the effects of Giardia infection on growth (weight and height) of the children.

Methods/Findings

Weight and height of 374 children aged 7–12 years were assessed before and after treatment of Giardia infection. The children were screened for Giardia parasite using trichrome staining technique. Demographic and socioeconomic data were collected via face-to-face interviews using a pre-tested questionnaire. Overall, 22.2% (83/374) of the children were found to be infected with Giardia. Nutritional status of children was assessed and the results showed that the mean weight and height were 23.9 kg (95% CI = 23.3, 24.5) and 126.6 cm (95% CI = 125.6, 127.5), respectively. Overall, the prevalence of severe underweight, stunting and wasting were 28.3%, 23.8% and 21.0%, respectively. Multiple linear regression analyses showed sex, Giardia infection and household monthly income as the significant determinants of weight while sex and level of mother''s education were the significant determinants of height. Weight and height were assessed at 3 and 6 months after treatment of Giardia infection. It was found that Giardia infection has a significant association with the weight of children but not with height.

Conclusions/Significance

This study reveals high prevalence of Giardia infection and malnutrition among Aboriginal children in rural Malaysia and clearly highlights an urgent need to identify integrated measures to control these health problems in the rural communities. Essentially, proper attention should be given to the control of Giardia infection in Aboriginal communities as this constitutes one of the strategies to improve the nutritional status of Aboriginal children.