Expression profile of lncRNAs and miRNAs in esophageal cancer: Implications in diagnosis,prognosis, and therapeutic response

Esophageal cancer is the seventh most common cancer worldwide. Although a number of environmental and lifestyle-related risk factors have been identified for this kind of cancer, the exact molecular mechanisms of tumor evolution have not been clarified yet. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) as important regulators of gene expression and chromatin configuration have essential roles in the pathogenesis of esophageal cancer. They have been shown to alter the function of cancer-related signaling pathways such as phosphoinositide 3-kinase/protein kinase B and Wnt pathway, thus they might modulate the response of patients to pathway-targeted therapies. Moreover, a number of lncRNAs, such as AFAP1-AS1, UCA1, HOTAIR, LOC285194, and TUSC7, are involved in conferring chemoresistant/radioresistant in esophageal cancer cells. A complex network of interaction exists between lncRNAs and miRNAs in the context of esophageal cancer. Finally, various panels of lncRNAs and miRNAs have been introduced that can predict the survival of esophageal cancer patients. In this review article, we summarize the recent findings regarding the role of miRNAs and lncRNAs in the pathogenesis of esophageal cancer with the special focus on their regulatory roles on signaling pathways, their potential as diagnostic/prognostic markers, and their relevance with therapeutic response.     

Life table parameters of large white butterfly Pieris brassicae (Lepidoptera: Pieridae) on different cabbage varieties

Effect of four different cole crops (Brassica oleracea var. botrytis, Brassica oleracea var. capitata, Brassica oleracea var. italica and Brassica oleracea var. viridis) on biological parameters of the large white butterfly Pieris brassicae was evaluated at temperature 26 ± 1 °C, 60 ± 5% R. H. and a photoperiod of 16: 8 (L:D) h. The shortest larval and pupal period stages were recorded on B. oleracea var. botrytis (22.18 ± 0.20 days) and (13.32 ± 0.17 days), respectively. The life span was longest on B. oleracea var. viridis (60.43 ± 2.34 days) and shortest on B. oleracea var. botrytis (50.19 ± 0.51 days). The highest percentage of larval and pupal mortality was observed on B. oleracea var. viridis (74%), and (53%), respectively. We found that P. brassicae prefers B. oleracea var. botrytis and B. oleracea var. capitata among cole crops; it is due to the lowest percentage of larval and pupal mortality and the highest rate of life table parameters, including survival rate (lx) and life expectancy (ex), which makes them to be susceptible varieties to this pest. Contrary, a longer developmental time on B. oleracea var. viridis may be attributed to poor nutritional status and reduced survival of the cohort, resulting in high rates of mortality, which was partial resistance to pest. Knowledge of the biology and life table parameters of P. brassicae on different cole crops could be effective in detecting and monitoring the pest infestation, variety selection and crop breeding.     

Biostratigraphy and paleoecology of the Oligo-Miocene succession in Fars and Khuzestan areas (Zagros Basin,SW Iran)

Paleontological and biostratigraphical studies on carbonate platform succession from southwest Iran documented a great diversity of shallow-water benthic foraminifera during the Oligocene–Miocene. Larger foraminifera are the main means for the stratigraphic zonation of carbonate sediments. The distributions of larger benthic foraminifera in two outcrop sections (Abolhayat and Lali) in the Zagros Basin, Iran, are used to determine the age of the Asmari Formation. Four assemblage zones have been recognized by distribution of the larger benthic foraminifera in the study areas. Assemblage 3 (Aquitanian age) and 4 (Burdigalian age) have not been recognized in the Abolhayat section (Fars area), due to sea-level fall. The end Chattian sea-level fall restricted marine deposition in the Abolhayat section and Asmari Formation replaced laterally by the Gachsaran Formation. This suggests that the Miocene part of the formation as recognized in the Lali section (Khuzestan area) of the Zagros foreland basin is not present in the Abolhayat outcrop. The distribution of the Oligocene larger benthic foraminifera indicates that shallow marine carbonate sediments of the Asmari Formation at the study areas have been deposited in the photic zone of tropical to subtropical oceans. Based on analysis of larger benthic foraminiferal assemblages and microfacies features, three major depositional environments are identified. These include inner shelf, middle shelf and outer shelf. The inner shelf facies is characterized by wackestone–packstone, dominated by various taxa of imperforate foraminifera. The middle shelf is represented by packstone–grainstone to floatstone with a diverse assemblage of larger foraminifera with perforate wall. Basinwards is dominated by argillaceous wackestone characterized by planktonic foraminifera and large and flat nummulitidae and lepidocyclinidae. Planktonic foraminifera wackestone is the dominant facies in the outer shelf.     

Synthesis of novel azo compounds containing 5(4H)-oxazolone ring as potent tyrosinase inhibitors

Six new azo dyes containing of 5(4H)-oxazolone ring were prepared by diazotization of 4-aminohippuric acid and coupling with N,N-dimethylaniline, 1-naphthol and 2-naphthol and condensation with 4-fluoro benzaldehyde or 4-trifluoromethoxy benzaldehyde. The new compounds were fully characterized by spectroscopic techniques. All synthesized compounds exhibited high tyrosinase inhibitory behavior. The results of mushroom tyrosinase inhibition assays indicate that the 4-trifluoromethoxy derivatives have high degrees of inhibition and N,N-dimethylaniline derivatives are better for tyrosinase inhibition than 1-naphthol and 2-naphthol derivatives. All synthesized azo compounds (4a–4f) showed the most potent mushroom tyrosinase inhibition, comparable to that of Kojic acid and l-mimosine, as reference standard inhibitors.     

Global 5-Hydroxymethylcytosine Levels Are Profoundly Reduced in Multiple Genitourinary Malignancies

Solid tumors are characterized by a plethora of epigenetic changes. In particular, patterns methylation of cytosines at the 5-position (5mC) in the context of CpGs are frequently altered in tumors. Recent evidence suggests that 5mC can get converted to 5-hydroxylmethylcytosine (5hmC) in an enzymatic process involving ten eleven translocation (TET) protein family members, and this process appears to be important in facilitating plasticity of cytosine methylation. Here we evaluated the global levels of 5hmC using a validated immunohistochemical staining method in a large series of clear cell renal cell carcinoma (n = 111), urothelial cell carcinoma (n = 55) and testicular germ cell tumors (n = 84) and matched adjacent benign tissues. Whereas tumor-adjacent benign tissues were mostly characterized by high levels of 5hmC, renal cell carcinoma and urothelial cell carcinoma showed dramatically reduced staining for 5hmC. 5hmC levels were low in both primary tumors and metastases of clear cell renal cell carcinoma and showed no association with disease outcomes. In normal testis, robust 5hmC staining was only observed in stroma and Sertoli cells. Seminoma showed greatly reduced 5hmC immunolabeling, whereas differentiated teratoma, embryonal and yolk sack tumors exhibited high 5hmC levels. The substantial tumor specific loss of 5hmC, particularly in clear cell renal cell carcinoma and urothelial cell carcinoma, suggests that alterations in pathways involved in establishing and maintaining 5hmC levels might be very common in cancer and could potentially be exploited for diagnosis and treatment.     

Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an <Emphasis Type="Italic">In Vitro</Emphasis> Evaluation Against <Emphasis Type="Italic">L. major</Emphasis> and <Emphasis Type="Italic">L. tropica</Emphasis>

Leishmaniasis is a worldwide disease that leads to high mortality and morbidity in human populations. Today, leishmaniasis is managed via drug therapy. The drugs that are already in clinical use are limited to a number of toxic chemical compounds and their parasite drug resistance is increasing. It is therefore essential, in order to circumvent the current difficulties, to design a new anti-leishmanial drug treatment strategy. Besides producing new, active anti-leishmanial entities, another promising strategy could be developing novel delivery systems and formulations of the existing pharmaceutical ingredients to improve drug efficacy. In the present study, paromomycin sulfate (PM), as one of the promising anti-leishmanial drugs, was formulated in solid lipid nanoparticles (SLN), and its in vitro efficacy was investigated against different strains of Leishmania using a MTT test, Parasite-Rescue-Transformation-Assay, SYTO Green staining, and fluorescent microscope imaging. The results show that PM-loaded SLN is significantly more effective than PM in inhibiting parasite propagation (P?<?0.05) and that cytotoxicity of PM-SLN formulations is size dependent. According to our results, delivery of the drugs to the macrophages via nanoparticle utilization seems to be an accessible and practical approach.     

CTNNBIP1 downregulation is associated with tumor grade and viral infections in gastric adenocarcinoma

Gastric cancer is a life-threatening disease; resulting from interaction among genetic, epigenetic, and environmental factors. Aberrant dysregulation and methylation changes in Wnt/β-catenin signaling downstream elements are a prevalent phenomenon encountered in gastric tumorigenesis. Also, viral infections play a role in gastric cancer development. CTNNBIP1 (β-catenin interacting protein 1) gene is an antagonist of Wnt signaling which binds to the β-catenin molecules. The CTNNBIP1 function as tumor suppressor gene or oncogene in different types of cancer is controversial. Moreover, its function and regulatory mechanisms in gastric cancer progression is unknown. In the present study, we examined CTNNBIP1 gene expression, the methylation status of the regulatory region of the gene, and their association with Epstein–Barr virus (EBV), and cytomegalovirus (CMV) and Helicobacter pylori infections in human gastric adenocarcinoma tissues in comparison with their adjacent nontumoral tissues. Our data revealed a significant downregulation of CTNNBIP1 in gastric tumors. Female patients showed lower level of CTNNBIP1 than males (p < 0.05). Also, decreased expression of CTNNBIP1 was markedly associated with well-differentiated tumor grades (p < 0.05). No methylation change was observed between tumoral and nontumoral tissues. Additionally, CTNNBIP1 down regulation was significantly associated with CMV infection (p < 0.05). In the absence of EBV infection, lower expression of CTNNBIP1 was observed. There was no association between H. pylori infection and CTNNBIP1 expression. Our findings revealed the tumor suppressor role for CTNNBIP1 in gastric adenocarcinoma. Interestingly, EBV and CMV infections modulate CTNNBIP1 expression.     

The effects of centrally administered apelin-13 on food intake, water intake and pituitary hormone release in rats

Apelin is the recently identified endogenous ligand for the G-protein-coupled receptor, APJ. Preproapelin and APJ mRNA are found in hypothalamic regions known to be important in the regulation of food and water intake, and pituitary hormone release. The effects of intracerebroventricular (ICV) administration of pyroglutamylated apelin-13 on food and water intake and pituitary hormone release in rats were investigated. Apelin-13 had little effect on food intake, but dose-dependently increased drinking behaviour and water intake at 1 h. Apelin-13 (10 nmol) increased water intake by up to sixfold compared to saline. Compared to saline control, apelin-13 (10 nmol) significantly increased plasma ACTH and corticosterone and decreased plasma prolactin, LH and FSH at 30 min. In vitro, apelin-13 stimulated the release of CRH and AVP from hypothalamic explants, but had no effect on NPY release. These results suggest that apelin may play an important role in the hypothalamic regulation of water intake and endocrine axes.