Search

Several microRNAs (miRNAs), including miR-221-5p, Let-7b-5p, miR-21-5p, miR-9-5p, miR-126-3p, and miR-222-3p, were recently found to be enriched in circulating exosomes of patients with non-small cell lung cancers (NSCLCs). These miRNAs distinguished cancer cases from controls with high precision and were predicted to modulate the expression of genes within the oncogenic LINE-1 regulatory network. To test this hypothesis, plasma exosomes from controls, early, and late-stage NSCLC patients were co-cultured with non-tumorigenic lung epithelial cells for 72 h and processed for measurements of gene expression. Exosomes from late-stage NSCLC patients markedly increased the mRNA levels of LINE-1 ORF1 and ORF2, as well as the levels of target miRNAs in naïve recipient cells compared to saline or control exosomes. Late-stage exosomes also modulated the expression of oncogenic targets within the LINE-1 regulatory network, namely, ICAM1, AGL, RGS3, RGS13, VCAM1, and TGFβ1. In sharp contrast, exosomes from controls or early-stage NSCLC patients inhibited LINE-1 expression, along with many of the genetic targets within the LINE-1 regulatory network. Thus, late-stage NSCLC exosomes activate LINE-1 and miRNA-regulated oncogenic signaling in non-tumorigenic, recipient lung bronchial epithelial cells. These findings raise important questions regarding lung cancer progression and metastasis and open the door for the exploration of new therapeutic interventions. [ABSTRACT FROM AUTHOR]

A growing number of studies have shown that microRNAs (miRNAs) can exert oncogenic or tumor suppressor activities in a variety of cancers, including lung cancer. Given their presence in exosome preparations, microRNA molecules may in fact participate in exosomal intercellular transfers and signaling. In the present study, we examined the profile of 25 circulating exosomal microRNAs in ostensibly healthy controls compared to patients with squamous cell lung cancers (SQCLC) or lung adenocarcinomas (LUAD). Eight miRNAs, namely, miR-21-5p, miR-126-3p, miR-210-3p, miR-221-3p, Let-7b-5p, miR-146a-5p, miR-222-3p, and miR-9-5p, were highly enriched in the cohort and selected for further analyses. All miRNAs were readily detected in non-small cell lung cancer (NSCLC) patients of both sexes at all cancer stages, and their levels in exosomes correlated with the clinicopathological characteristics of tumors. Thus, the presence of these miRNAs in circulating exosomes may contribute to the regulation of oncogenic activity in patients with NSCLC. [ABSTRACT FROM AUTHOR]

Heparin cofactor (HCII) is a member of serine protease inhibitors (SPIs) family of genes which play a fundamental physiological role in different biological processes including hemostasis. Therefore, this study aimed to cloning a partial nucleotide sequence of Nile Tilapia HCII cDNA and examine its expression level in the liver tissue following the intracoelomic injection of benzo-a-pyrene BaP. The cloned nucleotide sequence contained 972 bp representing a 666 bp of the Open Reading Frame (ORF) encodes for 221 amino acids and a stop codon and a 306 bp of the 3′ noncoding region. The amino acids sequence comparison and phylogenetic tree analysis showed a close relationship between tilapia and Pundamilia nyererei serpind1 sequences. Realtime-PCR results showed high expression level (6.2) of Serpind1 mRNA in the liver of the BaP-treated fish compared with the control group suggesting the physiological role of HCII in tilapia. The study proposed the use of tilapia fish as a mammalian hemostasis model depending on the hemostatic genes homology analysis. [ABSTRACT FROM AUTHOR]

This study was attempted to figure out the hypolipidemic and hypoglycemic effects of cinnamon (CIN) and sesame oil on rats fed high-fat diet (HFD). It was conducted on 36 rats, divided into control (12) and high fed diet (24) for 7 weeks, and then 6 animals from each group were killed for collection of samples. The remaining rats of HFD group (18) were subdivided into three subgroups (6 rats for each): recovery (fed standard diet only), Cinnamon (CIN) group and sesame group. Lipid profile and glucose hemostasis, TNF-α and C-reactive protein (CRP) were detected in all groups. The histology and immunohistochemistry of liver with nuclear factor kappa B (NF-kB), in addition to DNA fragmentation assay were carried out. High fat diet (HFD) rats showed an increase in cholesterol, triglycerides, LDL-c, glucose, insulin resistance. Also, CRP and TNF-α in serum and immuneexpression of NF-kB in liver were elevated. Both CIN and sesame were completely restored LDL-c, glucose, HOMA -IR, CRP and TNF-α and partially restored cholesterol, triglycerides (TG) and insulin resistance. CIN enhances HDL-C level. Histologically, lipid droplets, inflammatory and Kupffer cells were increased in HFD. The histological and immunohistochemical profiles were improved in CIN group and sesame group but CIN was much better than sesame. No DNA fragmentation was observed in any of the five groups, which indicated hypolipidemia however; CIN improves the histological profile more than sesame oil. [ABSTRACT FROM AUTHOR]

Exosomes are secreted membrane-bound vesicles containing a cargo of curated nucleic acids, proteins, and lipids that can alter gene expression in recipient cells. Toxic agents can alter exosome synthesis and bioactive cargo composition, thus allowing exosomes to serve as biomarkers of exposure and response. While human and animal studies have identified exosome biomarkers of organ toxicity, in vitro models are ideal to examine biological mechanisms of exosome function. Here, we discuss the importance of exosomes in toxicology research and describe applications of in vitro models in advancing our understanding of their role in exposure-associated disease. This discussion of new research frontiers is in commemoration of the invaluable contributions of Dr. Daniel Acosta to the field of in vitro biology and toxicology. Emerging studies have implicated exosomes as mediators of neurodegeneration by shuttling pollutant-induced pathogenic proteins and miRNAs from afflicted neurons to neighboring cells. Exosomes also provide a mechanistic link between inhalation exposures and airway inflammation, remodeling, and systemic effects. Exosomes provide the means for toxic agents to initiate oncogenic transformation and create favorable tumor microenvironments. Furthermore, exosome-mediated drug delivery can alter drug pharmacologic profiles. Expansion in this field using in vitro models is essential to unlock the potential applications of exosome biology in toxicology., Competing Interests: Conflict of interest The authors declare no conflict of interest. In addition, Drs. Bowers and Ramos filed a patent “Exosome-based Liquid Biopsy” pending., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The present study was carried out to evaluate the toxopathological effects and macro-DNA damage of Aflatoxin B1 (AFB1) in pregnant rats at a dose of 1mg/kg. body wt., given from 6th to 15th day of gestation. The effects and damage are represented by histopathological changes and different types of chromosomal aberrations in dams, in addition to teratogenic changes in the feti. Pregnant dams revealed a significant decrease in their body weights and gross enlargement of the liver. Histologically, the liver showed necrotic areas and congested central vein. The kidneys revealed interstitial hemorrhages, renal casts, degeneration and necrosis. The lungs revealed lymphocytic infiltrates in the interstitial tissue, while the spleen revealed lymphoid depletion. Chromosomal analysis revealed both structural and numerical chromosomal aberration, including centromeric attenuations, chromatid gaps, chromatid breaks, end-to-end associations, fragments, ring chromosomes, deletions, dicentric chromosomes, chromosomal fusions, centric fusions, stickness and hypoployploidy. Centromeric attenuations and end-to-end associations were more frequent than other chromosomal aberrations. Concerning the teratogenic effects in the fetuses, the toxin induced multiple skeletal anomalies. These anomalies included incomplete ossification of skull bones and failure of ossification of long and flat bones., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

CYP1C is the newest member of the CYP1 family of P450s; however, its physiological significance, inducers, and metabolic functions are unknown. In this study, a new complementary DNA of the CYP1C subfamily encoding CYP1C1 was isolated from Nile tilapia (Oreochromis niloticus) liver after intracoelomic injection with benzo-a-pyrene (BaP). The full-length cDNA was 2223 base pair (bp) long and contained an open reading frame of 1581 bp encoding a protein of 526 amino acids and a stop codon. The sequence exhibited 3' non-coding region of 642 bp. The deduced amino acid sequence of O. niloticus CYP1C1 shows similarities of 86, 82.5, 79.7, 78.7, 77.8, 75.5, 69.6 and 61.3% with scup CYP1C1, killifish CYP1C1,1C2, Japanese eel CYP1C1, zebra fish CYP1C1, common carp CYP1C1, scup CYP1C2, common carp CYP1C2 and zebra fish CYP1C2, respectively. Phylogenetic tree based on the amino acids sequences clearly shows tilapia CYP1C1 and scup CYP1C1 to be more closely related to each other than to CYP1C genes from other species. Furthermore, for measuring BaP induction of CYP1C1 mRNA in different organs of tilapia (O. niloticus), β-actin gene as internal control was selected based on previous studies to assess their expression variability. Real time RCR results revealed that there was a large increase in CYP1C1 mRNA in liver (43.1), intestine (5.1) and muscle (2.4)., (Copyright © 2011 Elsevier B.V. All rights reserved.)