The Effect of miR-145-5p, DANCR and NRAS Expression Levels on the Survival Rate of Colorectal Cancer Patients.

BACKGROUND: The prevalence of colorectal cancer (CRC) has been increasing in the world. There are different factors for colorectal cancer, and changes in the levels of gene expression such as miR-145-5p, DANCR and NRAS can be one of the factors. METHODS: The case-control study was performed on 40 CRC specimens and 40 adjacent healthy tissues. Fresh tumor and tumor-free adjacent tissue samples were obtained from patients who underwent the surgical operation as a conventional treatment procedure. After tumor resection, the specimens were immediately frozen in liquid nitrogen and stored at -80°C until further investigation. Cox regression was used to get the hazard ratios. RESULTS: The mean ± SD age of the patients was 62.45± 12.89 years. Of these, 62.5% were males. The risk of death from CRC in patients with low miR-145-5p levels is about 10 times higher than the high expression levels (HR = 10.759, P = 0.009). High expression levels of NRAS can increase the risk of CRC death up to 4 times (HR = 4.12, P = 0.045). The study did not show a relationship between DANCR expression levels and death risk from CRC (HR = 1.582, P = 0.439). CONCLUSION: These expression levels revealed that miRNA-145-5p and NRAS can be utilized as diagnostic biomarkers in colorectal cancer death. This may also introduce the microRNAs as colorectal cancer therapeutic targets.

Assessment of lncRNA DANCR, miR-145-5p and NRAS axis as biomarkers for the diagnosis of colorectal cancer.

Recent evidence reveals that miRNA sponges neutralize miRNAs activity by binding to miRNAs and sequester them from their relevant targets to regulate expression. The detailed mechanisms of sponge RNAs in colorectal cancer remain to be exactly determined. In this study DANCR, miR-145-5p, NRAS axis was evaluated and the diagnostic value of these targets was assessed in colorectal cancer patients. A case-control study was carried out on 40 samples of tumor tissues and 40 adjacent tissues. Total RNA was extracted, and then, the expression level of DANCR, miR-145-5p and NRAS was evaluated using qRT-PCR. In addition, the sensitivity and specificity of these markers were evaluated by receiver operating characteristic (ROC) curve analysis. Our results revealed that the expression level of DANCR was significantly upregulated in colorectal cancer tissues (p < 0.001). It was demonstrated that DANCR could regulate NRAS expression by sponging miR-145-5 in colorectal cancer patients. Furthermore, the mean expression of miR-145-5p (p < 0.001) and NRAS (p < 0.001) was significantly different between tumor and normal tissue. A significant correlation was observed between DANCR and miR-145-5p (p = 0.001), and also between miR-145-5p and NRAS (p < 0.001). Sensitivity and specificity value for DANCR, miR-145-5p and NRAS were (0.875 and 0.725), (0.875 and 0.745), and (0.877 and 0.694), respectively. According to the values of sensitivities and specificity of DANCR, miR-145-5p and NRAS, confirmed with ROC curve analysis, these biomarkers may be useful in the screening and differentiating between tumor and control sample in colorectal neoplasm.

Promoted chondrogenesis of hMCSs with controlled release of TGF-ß3 via microfluidics synthesized alginate nanogels.

The field of cartilage tissue engineering has been evolved in the last decade and a myriad of scaffolding biomaterials and bioactive agents have been proposed. Controlled release of growth factors encapsulated in the polymeric nanomaterials has been of interest notably for the repair of damaged articular cartilage. Here, we proposed an on-chip hydrodynamic flow focusing microfluidic approach for synthesis of alginate nanogels loaded with the transforming growth factor beta 3 (TGF-ß3) through an ionic gelation method in order to achieve precise release profile of these bioactive agents during chondrogenic differentiation of mesenchymal stem cells (MSCs). Alginate nanogels with adjustable sizes were synthesized by fine-tuning the flow rate ratio (FRR) in the microfluidic device consisting of cross-junction microchannels. The result of present study showed that the proposed approach can be a promising tool to synthesize bioactive -loaded polymeric nanogels for applications in drug delivery and tissue engineering.

Giardia lamblia assemblages A and B isolated from symptomatic and asymptomatic persons in Hamadan, west of Iran.

Giardia is a very abundant organism bringing about diarrhoea in human beings. The focus of this analysis was the detection of Giardia lamblia assemblages in human stool specimens in Hamadan, west of Iran, as well as the association between obtained assemblages and clinical symptoms. Faecal samples of 4066 individuals admitted to the medical and health care facilities in Hamadan were inspected microscopically for the existence of Giardia cysts/trophozoites, and the clinical symptoms of the patients were recorded. The DNA of positive samples was isolated from and the nucleotide sequences of both glutamate dehydrogenase (gdh) (n = 15) and triose phosphate isomerase (tpi) (n = 8) genes were analyzed. In direct microscopy, a total of sixty-four samples (1.6%), were considered as positive for G. lamblia cysts or trophozoites. The sequence analysis showed that 18 out of 23 sequenced isolates (78.2%) were assemblage A and 5 (21.7%) were assemblage B. Clinical symptoms were observed in 44.4% and 40% of patients with assemblages A and B, respectively. Overall, the predominant assemblage A detected in the tested samples along with bioinformatics analysis suggest a potential zoonotic transmission in the region of the study. Although advanced analyses are necessary to understand the foundation and path of the infection, it seems that more sanitary regulations regarding contact with livestock and pet animals are essential.

Cerium Oxide Nanoparticle Effects on Paraoxonase-1 Activity and Oxidative Toxic Stress Induced by Malathion: A Potential Antioxidant Compound, Yes or No?

Cerium oxide nanoparticles (CeNPs) are one of the most widely used and important nanoparticles in addition to possessing strong antioxidative properties and inhibiting free radicals. Paraoxonase-1 (PON1) is one of the enzymes that protect the body against damage caused by oxidative stress. The purpose of this study was to investigate the effect of CeNPs on the activity of PON1 as well as biomarkers of oxidative stress in the toxicity of malathion. 48 Albino Wistar male rats with weight range of 180-250 g were randomly divided into 8 groups, Group 1: healthy control, injection of normal saline, Group 2: administration by the malathion 100 mg/kg/day, Group 3: treated with CeNPs 15 mg/kg/day, Group 4: treated with CeNPs 30 mg/kg/day, Group 5: combination of malathion with dose of 100 mg/kg/day and CeNPs 15 mg/kg, Group 6: combination of malathion with dose of 100 mg/kg/day and CeNPs 30 mg/kg for 14 days and 24 h after termination of treatment period, serum and liver tissue samples were collected from all rats. Biochemical test of PON1 activity, oxidative stress biomarkers including total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), were carried out. Malathion reduced plasma TTG levels, TAC and increased LPO in malathion group. However, CeNPs increased TTG, TAC and reduced PON1 activity. Results showed that CeNPs alone had antioxidant properties while with malathion it shows different properties.

The effect of salusin-ß on expression of pro- and anti-inflammatory cytokines in human umbilical vein endothelial cells (HUVECs).

BACKGROUND: Atherosclerosis is one of the predominant causes of cardiovascular disease (CVD). Several studies indicated the significant pathophysiological role of salusin-ß in atherosclerosis. Cytokines are involved in all stages of atherosclerosis. Therefore, we aimed to assess the effect of salusin-ß on interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18) (as inflammatory cytokines) and interleukin 1Ra (IL-1Ra) (as anti-inflammatory cytokines) levels in human umbilical vein endothelial cells (HUVECs). METHODS: The HUVECs were cultured in HUVEC completed medium and treated with different doses of salusin-ß for 6 and 12 hours. For the investigation of nuclear factor Æ™ß (NF-ƙß) signaling pathway involvement, cells were treated in the presence or absence of Bay 11-7082 (as NF-Æ™ß inhibitor). The mRNA expression and protein level of cytokines were measured by a real-time polymerase chain reaction (PCR) system and enzyme-linked immunosorbent assay (ELISA) method, respectively. RESULTS: Salusin-ß increased mRNA expression and protein level of IL-6, IL-8 and IL-18. This protein decreased mRNA and protein level of IL-1Ra in HUVECs. NF-Æ™ß signaling pathway was involved in the up-regulatory effect of salusin-ß on mRNA expression of pro-inflammatory cytokines. The down-regulatory effect of salusin-ß on IL-1Ra expression could not be influenced by Bay 11-7082 pre-treatment. CONCLUSION: It seems that salusin-ß may participate in a cascade pathway in vascular inflammation. Our findings suggested that salusin-ß has potential use as a therapeutic target for atherosclerosis.

The Potential Use of Peptides in Cancer Treatment.

Conventional chemotherapeutic drugs have significant limitations. For example, tumors may develop resistance, cancers may relapse after treatment, and the drugs may induce secondary malignancies in the treatment of metastatic cancer. There is still a great need for drugs that are able to destroy cancer cells selectively, that is, to effectively treat slow-growing and dormant cells without being affected by chemoresistance mechanisms. A growing number of studies indicate that peptides may be beneficial for drug discovery and development. Peptides offer minimal immunogenicity, excellent tissue penetrability, low-cost manufacturability, and ease of modification for enhancing in vivo stability and biological activity, properties which make them ideal candidates for cancer treatment. This review highlights recent advances in and future prospects for the application of peptides as therapeutic agents for cancer therapy. We discuss the application of peptides in cancer therapy, alone and in combination with other peptides or small-molecule chemotherapeutic drugs, for use in targeted cancer therapy. Furthermore, we consider the use of peptides as a carrier for targeted molecular imaging in the diagnosis and follow-up treatment of cancer. This account also reviews the challenges of using peptide drugs and ways to overcome these limitations. The results obtained in studies presented in this paper indicate that peptides are promising candidates for targeted cancer therapy.

Salusin-α Attenuates Inflammatory Responses in Vascular Endothelial Cells.

Atherosclerosis accounts for numerous cardiovascular diseases, and cytokines have a critical role in acceleration or suppression of disease. Salusin-α presents a new class of bioactive peptides that can have anti-atherogenic properties. Therefore, the effects of salusin-α on the expression of some pro- and anti-inflammatory cytokines and on TNF-α-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs) were examined. The involvement of the NF-κB pathway in effects of salusin-α in HUVECs was checked using Bay 11-7082 as an NF-κB inhibitor. The mRNA expression of pro-inflammatory cytokines including IL-6, IL-8, and IL-18 and anti-inflammatory cytokine IL-1Ra was assessed by real-time PCR. The protein levels of cytokines were measured by the ELISA method. Salusin-α suppressed both mRNA and protein expression of pro-inflammatory cytokines and induced mRNA and protein expression of IL-1Ra in HUVECs. Salusin-α suppressed TNF-α-induced inflammatory responses in HUVECs. The down-regulatory or up-regulatory effects of salusin-α on expression of cytokines could not be influenced by Bay 11-7082 pretreatment. Our findings indicate anti-inflammatory effects of salusin-α and suggest a novel peptide-based therapeutic strategy for atherosclerosis.

Comparison of Three Types of Mesenchymal Stem Cells (Bone Marrow, Adipose Tissue, and Umbilical Cord-Derived) as Potential Sources for Inner Ear Regeneration.

In this review, we compared the potential of mesenchymal stem cells derived from bone marrow, adipose tissue and umbilical cord as suitable sources for regeneration of inner ear hair cells and auditory neurons. Our intensive literature search indicates that stem cells in some of adult mammalian tissues, such as bone marrow, can generate new cells under physiological and pathological conditions. Among various types of stem cells, bone marrow-derived mesenchymal stem cells are one of the most promising candidates for cell replacement therapy. Mesenchymal stem cells have been reported to invade the damaged area, contribute to the structural reorganization of the damaged cochlea and improve incomplete hearing recovery. We suggest that bone marrow-derived mesenchymal stem cells would be more beneficial than other mesenchymal stem cells.