No abstract

With the development of technologies such as microarrays and RNA deep sequencing, long noncoding RNAs (lncRNAs) have become the focus of cancer investigations. LncRNAs, nonprotein-coding RNA molecules longer than 200 nucleotides, are dysregulated in many human diseases, especially in cancers. Recent studies have demonstrated that lncRNAs play a key regulatory role in gene expression and cancer biology through diverse mechanisms, including chromosome remodeling and transcriptional and post-transcriptional modifications. The expression levels of specific lncRNAs are attributed to prognosis, metastasis, and recurrence of cancer. LncRNAs are often involved in various biological processes, such as regulation of alternative splicing of mRNA, protein activity, and epigenetic modulation or silencing of the microRNAs, via discrete mechanisms. Deregulated levels of lncRNAs are shown in diverse tumors, including breast cancer. Based on latest research data, the tissue-specific expression signature of lncRNAs may represent the potential to discriminate normal and tumor tissue or even the different stages of breast cancer, which makes them clinically beneficial as possible biomarkers in the diagnosis and prognosis or therapeutic targets. In this brief review, we summarize some recent researches in the context of lncRNAs' roles in breast cancer pathogenesis and their potential to serve as diagnostic, predictive, and prognostic biomarkers and novel targets for breast cancer treatment.

No abstract

BACKGROUND: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the first cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treat it. Stem cell-based therapies as a regeneration strategy cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. METHODS: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. RESULTS: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. CONCLUSIONS: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.

Stem cell-based therapies is a promising approach for regenerative therapy in various diseases. Some obstacles remain to be solved before clinical application of the cell therapy is realized, including increasing the survival of transplanted stem cells, reducing loss of transplanted cells, and maintaining adequate vascular supply. Recently, stem cell preconditioning with chemical and pharmacological agents has been shown to increase therapeutic efficacy. The present study investigated the effect of endothelin-1 (ET-1) on survival, angiogenesis, and migration of mesenchymal stem cells (MSCs), in vitro. MSCs were treated with various concentrations of ET-1 and the expression of cyclooxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 2 (CCR2), vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), angiopoietin-4 (Ang-4) and matrix metalloproteinase-2 (MMP-2) were examined. Caspase 3 activity and prostaglandin E2 (PGE2) were determined by ELISA assay. MSCs migration and tube formation potential were assessed using scratch test and three dimensional vessel formation assay. ET-1 enhanced the MSCs viability. In ET-1- treated MSCs, expression of COX-2, HIF-1, CXCR4, CCR2, VEGF, Ang-2, Ang-4 and MMP-2 were increased compared to control groups. Elevation of all these genes were reversed by celecoxib (50 μmol/L), a selective COX-2 inhibitor. PGE2 generation, MSCs migration and tube formation were enhanced by ET-1 conditioning, whereas caspase-3 activity was reduced in these cells, compared to the control group. The results presented here reveal that preconditioning of MSCs with ET-1 has strong cytoprotective effects through activation of survival signalling molecules and trophic factors.

No abstract

Colorectal cancer (CRC) is in the third place of the most common cancers. Certain risk factors can increase the development of CRC, including diet and inheritance. Several studies have shown that there is a potential link between obesity and CRC. Adipose tissue is known to be a largest endocrine organ in the body, with the ability to produce various cytokines including adiponectin. Two types of adiponectin receptor, AdipoR1 and AdipoR2, have been detected in various cancer tissues such as CRC. There is mounting evidence that AdipoR1 signaling occurs mainly through 5′ AMP-activated protein kinase (AMPK) and adiponectin inhibits colorectal cancer cell growth via activation of AMPK, thereby suppression of the mammalian target of rapamycin (mTOR) pathway. Thus, adiponectin replacement-based therapies may represent a novel approach in CRC cell growth inhibition in early stages. AdipoRon is an adiponectin-like synthetic small molecule that activated both adiponectin receptors 1 and 2. We hypothesize that AdipoRon has antiproliferative effects of adiponectin and may suppress the CRC cell growth. With clarification of this drug's role in CRC, it can be used as chemoprevention in patients at risk of developing the disease.

Background Type A influenza viruses are contagious and even life-threatening if left untreated. So far, no broadly protective vaccine is available due to rapid antigenic changes and emergence of new subtypes of influenza virus. In this study, we exploited bioinformatics tools in order to design a subunit chimeric vaccine from the antigenic and highly conserved regions of HA and M2 proteins of H7N9 subtype of influenza virus. We used mucosal adjuvant candidates, including CTxB, STxB, ASP-1, and LTB to stimulate mucosal immunity and analyzed the combination of HA2, M2e, and the adjuvant. Furthermore, to improve the antigen function and to maintain their three-dimensional structure, 12 different linkers including six rigid linkers and six flexible linkers were used. The 3D structure model was generated using a combination of homology and ab initio modeling methods and the molecular dynamics of the model were analyzed, either. Results Analysis of different adjuvants showed that using CtxB as an adjuvant, results in higher overall vaccine stability and higher half-life among four adjuvant candidates. Fusion of antigens and the CTxB in the form of M2e-linker-CTxB-linker-HA2 has the most stability and half life compared to other combination forms. Furthermore, the KPKPKP rigid linker showed the best result for this candidate vaccine among 12 analyzed linkers. The changes in the vaccine 3D structure made by linker insertion found to be negligible, however, although small, the linker insertion between the antigens causes the structure to change slightly. Eventually, using predictive tools such as Ellipro, NetMHCpan I and II, CD4episcore, CTLpred, BepiPred and other epitope analyzing tools, we analyzed the conformational and linear epitopes of the vaccine. The solubility, proteasome cleavage sites, peptidase and potential chemical cutters, codon optimization, post translational modification were also carried out on the final vaccine. Conclusions It is concluded that M2e-Linker-CTxB-Linker-HA2 combination of chimeric vaccine retains its 3D structure and antigenicity when KPKPKP used as linker and CTxB used as adjuvant.