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Breast cancer is categorized as the most widespread cancer type among women globally. On-time diagnosis can decrease the mortality rate by making the right decision in the therapy procedure. These features lead to a reduction in medication time and socioeconomic burden. The current review article provides a comprehensive assessment for breast cancer diagnosis using nanomaterials and related technologies. Growing use of the nano/biotechnology domain in terms of electrochemical nanobiosensor designing was discussed in detail. In this regard, recent advances in nanomaterial applied for amplified biosensing methodologies were assessed for breast cancer diagnosis by focusing on the advantages and disadvantages of these approaches. We also monitored designing methods, advantages, and the necessity of suitable (nano) materials from a statistical standpoint. The main objective of this review is to classify the applicable biosensors based on breast cancer biomarkers. With numerous nano-sized platforms published for breast cancer diagnosis, this review tried to collect the most suitable methodologies for detecting biomarkers and certain breast cancer cell types.

Most eukaryotic cells secrete extracellular vesicles (EVs), which contribute to intracellular communication through transferring different biomolecules such as proteins, RNAs, and lipids to cells. Two main types of EVs are exosomes and microvesicles. Exosomes originate from multivesicular bodies, while microvesicles are shed from the plasma membrane. Mechanisms of exosomes and microvesicle biogenesis/trafficking are complex and many molecules are involved in their biogenesis and secretion. Tumor-derived EVs contain oncogenic molecules that promote tumor growth, metastasis, immune surveillance, angiogenesis, and chemoresistance. A growing body of evidence indicates various compounds can inhibit biogenesis and secretion of EVs from cells and several experiments were conducted to use EVs-inhibitors for understanding the biology of the cells or for understanding the pathology of several diseases like cancer. However, the nontargeting effects of drugs/inhibitors remain a concern. Our current knowledge of EVs biogenesis and their inhibition from tumor cells may provide an avenue for cancer management. In this review, we shed light on exosomes and microvesicles biogenesis, key roles of tumor-derived EVs, and discuss methods used to inhibition of EVs by different inhibitors.

The combination of nanotechnology and stem cell biology is one of the most promising advances in the field of regenerative medicine. This novel combination has widely been utilized in vitro settings in an attempt to develop efficient therapeutic strategies to overcome the limited capacity of the central nervous system (CNS) in replacing degenerating neural cells with functionally normal cells after the onset of acute and chronic neurological disorders. Importantly, biomaterials, not only, enhance the endogenous CNS neurogenesis and plasticity, but also, could provide a desirable supportive microenvironment to harness the full potential of the in vitro expanded neural stem cells (NSCs) for regenerative purposes. Here, first, we discuss how the physical and biochemical properties of biomaterials, such as their stiffness and elasticity, could influence the behavior of NSCs. Then, since the NSCs niche or microenvironment is of fundamental importance in controlling the dynamic destiny of NSCs such as their quiescent and proliferative states, topographical effects of surface diversity in biomaterials, that is, the micro-and nano-patterned surfaces will be discussed in detail. Finally, the influence of biomaterials as artificial microenvironments on the behavior of NSCs through the specific mechanotransduction signaling pathway mediated by focal adhesion formation will be reviewed.

Here, the regenerative potential of menstrual blood-derived mesenchymal stem cells (MenSCs) was examined on restoration of premature ovarian failure (POF) ovaries in rats' POF model. Freshly isolated CD146+ MenSCs using magnetic-activated cell storing method were immediately injected into ovaries of POF rats. Four and eight weeks after cell administration, both ovarian tissues were sampled for histological examination and the expression of fibrosis-related genes. Serum samples were also prepared for hormonal analysis. At the endpoint, mating trials were performed to assess the fertility of POF rats following MenSC transplantation. Histopathological examination revealed the induction of POF after Ceftriaxone injection by increasing atretic follicles and abnormal morphologies. MenSCs transplantation increased the number of normal follicles and coincided with the reduction of follicular atresia. Biochemical analyses exhibited the reduction and increase of systemic follicle-stimulating hormone (FSH) and E2 respectively after MenSCs transplantation compared to the POF rats (P < .05). No significant differences in anti-mullerian hormone (AMH) blood levels were detected in this study between POF controls and MenSCs-treated rats. We noted moreover the transcriptional up-regulation of Smad 2, 4, and TGF-β1 in POF rats, and these values were decreased after MenSCs transplantation (P < .01). By contrast, the RNA expression of Smad 6 remained increased in both pre- and post-treatment with MenSCs groups (P < .05). Finally, we found an increase in neonate births in POF rats treated with MenSCs, and that this feature was associated with ovarian rejuvenation through amelioration of fibrosis. These data showed that MenSCs are promising cell lineage for the alleviation of POF in the rat model by controlling the fibrosis rate.

NEW FINDINGS What is the central question of this study? The aim of the experiment was to highlight the regenerative capacity of bone marrow Kit+ cells in the restoration of asthmatic pulmonary function in the rat model. What is the main finding and its importance? Data showed that these cells were recruited successfully to the asthmatic niche after intratracheal administration and accelerated the regeneration of asthmatic lungs by the modulation of inflammation via the control of Gata3 and Tbx21 expression, leading to decreased tracheal responsiveness to methacholine and reduction of pathological remodelling. ABSTRACT Allergic asthma is a T helper (Th) 2 immunological disorder with consequential uncontrolled inflammatory responses. There is an increasing demand to use new methods for the treatment of asthma based on modulation of the Th2-to-Th1 ratio in favour of the Th1 population. Accordingly, we decided to evaluate the effects of intratracheal administration of Kit+ bone marrow cells on tracheal responsiveness and the expression of Gata3 and Tbx21 genes. Forty male Wistar rats were allocated randomly into four experimental groups: healthy rats (control group), sensitized rats (OVA group), sensitized rats receiving Kit- cells (OVA+Kit- group) and sensitized rats receiving Kit+ cells (OVA+Kit+ group). Total and differential white blood cell counts, tracheal responsiveness to cumulative methacholine concentrations and histopathological analysis were evaluated. The results showed a statistically significant increase in total white blood cell, eosinophil and neutrophil counts, tracheal contractility, Gata3 expression and prototypical histopathology of asthma. Along with these conditions, we found that the number of lymphocytes was decreased and expression of Tbx21 diminished in sensitized rats compared with control animals. Monitoring of labelled tagged cells confirmed successful engraftment of transplanted cells in pulmonary tissue. Juxtaposition of Kit+ cells changed the blood leucogram closer to the control values. Kit+ cells increased the expression of Tbx21 and suppressed Gata3 (P

Tumor cells secrete extracellular vesicles (EVs) for intercellular communication. EVs by transporting different proteins, nucleic acids, and lipids contribute to affect target cell function and fate. ‎EVs which originate directly from multivesicular bodies so-called exosomes have dramatically fascinated the attention of researchers owing to their ‎pivotal roles in the tumorigenesis. Breast cancer, arising from milk-producing cells, is the most identified cancer among women and has become the leading cause of cancer-related death in women globally. Although different therapies are applied to eliminate breast tumor cells, however, the efficient therapy and survival rate of patients remain challenges. Growing evidence ‎shows exosomes from breast cancer cells contribute to proliferation, metastasis, angiogenesis, chemoresistance, and also radioresistance and, thus carcinogenesis. Additionally, these exosomes may serve as a cancer treatment tool because they are a good candidate for cancer diagnosis (as biomarker) and therapy (as drug-carrier). Despite recent development in the biology of tumor-derived exosomes, the detailed mechanism of tumorigenesis, and exosome-based cancer-therapy remain still indefinable. Here, we discuss the key function of breast cancer-derived exosomes in tumorgenesis and shed light on the possible clinical application of these exosomes in breast cancer treatment.

Ischemic stroke is characterized by extensive neuronal loss, glial scar formation, neural tissue degeneration that leading to profound changes in the extracellular matrix, neuronal circuitry, and long‐lasting functional disabilities. Although transplanted neural stem cells (NSCs) can recover some of the functional deficit after stroke, retrieval is not complete and repair of lost tissue is negligible. Therefore, the current challenge is to use the combination of NSCs with suitably enriched biomaterials to retain these cells within the infarct cavity and accelerate the formation of a de novo tissue. This study aimed to test the regenerative potential of polylactic‐co‐glycolic acid‐polyethylene glycol (PLGA‐PEG) micelle biomaterial enriched with Reelin and embryonic NSCs on photothrombotic stroke model of mice to gain appropriate methods in tissue engineering. For this purpose, two sets of experiments, either in vitro or in vivo models, were performed. In vitro analyses exhibited PLGA‐PEG plus Reelin‐induced proliferation rate (Ki‐67+ NSCs) and neurite outgrowth (axonization and dendritization) compared to PLGA‐PEG + NSCs and Reelin + NSCs groups (p

Heat shock proteins (HSPs) participate in the regulation of different cell activities in response to stimuli. By applying different strategies, the modulation of heat shock proteins is at the center of attention. Conventional delivery approaches are not fully encouraged due to cytotoxicity and immunogenicity issues. Exosomes are touted as bio-shuttles for delivery of distinct biomolecules inside the cells. Here, we aimed to HSP27 small interfering RNA (siRNA)-tagged exosomes for the inhibition of Hsp27 in human neuroblastoma cell line SH-SY5Y and explored differentiation into neuron-like cells. Exosomes were isolated, characterized by scanning electron microscope (SEM) and CD63 then enriched with siRNA against Hsp27. Neuroblastoma cells were incubated with exosomes carrying siRNA for 48 hr. Exosome uptake was monitored by immunofluorescence assay. The cell viability and proliferation were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine/5-bromo-2'-deoxyuridine incorporation assays. The ability of cells to form colonies was evaluated by clonogenic assay. The cell potential to express NeuN, a mature neuron factor, was studied by flow cytometry analysis. SEM showed the nano-sized particles and a high level of CD63 after enrichment. Immunofluorescence imaging revealed an appropriate transfection rate in cell exposed to Hsp27 siRNA tagged exosomes. The cell viability and proliferation were reduced compared to cells received nude exosomes ( p < 0.05). Clonogenic activity of cells was diminished by the inhibition of Hsp27. Flow cytometry analysis revealed that the inhibition of Hsp27 prohibited NeuN content, showing the maturation of SH-SY5Y cells to mature cells compared to control. These data confirmed that exosomes could be used as appropriate bio-shuttles for the inhibition of Hsp27-aborted cell differentiation toward mature neuron.

Ovarian cancer is associated with a high percentage of recurrence of tumor and resistance to chemotherapy. Cancer stem cells (CSCs) form a rare population with a significant capacity to begin and expand malignant diseases. Eliminating the drug resistance of CSCs by factors that have fewer side effects to the patient is vital. To investigate the effect of resveratrol (RES) and doxorubicin (DOX) on drug resistance and apoptosis of CSCs; at the first, isolation of CSCs from SKOV3 ovarian carcinoma cells and their dosage adjustment (IC50 ) with RES and DOX was performed. Then, isolated CSCs were treated with RES and DOX IC 50 of 55 and 250 nM, respectively. Subsequently, their effects on drug resistance and cell death were evaluated using real-time polymerase chain reaction, rhodamine 123 uptakes. The results of the present study demonstrated that treatment of SKOV3 with 55 μM of RES and 250 nM of DOX simultaneously increased cell viability in CSCs to DOX after 24 and 48 hours by increasing the expression of Bcl-2-associated X protein (BAX) and caspase-3 genes, and decreased the expression and function of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) genes indicated by intracellular the rhodamine 123 content. Treatment of RES could increase the activity of DOX cell viability in CSCs originated from SKOV3 ovarian carcinoma and decrease drug resistance capacity to DOX.

Murine c-kit+ cardiac cells were isolated and enriched by magnetic activated cell sorting technique. c-kit+ cells viability and colony-forming activity were evaluated by MTT and clonogenic assay. c-kit+ cells were exposed to endothelial, pericyte, and cardiomyocyte induction media containing 30mM glucose for 7 days. We monitored the level of endothelial (VE-cadherin, CD31, and vWF), pericyte (NG2 , α-SMA, and PDGFR-β), and cardiomyocyte markers (cTnT) using flow cytometry, real-time Polymerase Chain Reaction (PCR), and Enzyme-Linked Immunosorbent Assay (ELISA) analyses. Ultrastructural changes were studied by transmission electron microscopy (TEM) in cells treated with 5-Azacytidine and 30mM glucose. Matrigel plug assay was performed to determine the angio/cardiogenic property of c-kit+ cells in a diabetic mouse model. Glucose of 30mM decreased c-kit+ cells viability and clonogenicity (P < 0.05). The transdifferentiation capacity of c-kit+ cells into the endothelial lineage, pericytes, and cardiomyocytes were reduced through the inhibition of related genes (P < 0.05). TEM analysis revealed cardiomyocyte differentiation rate in c-kit+ cells coincided with an increased intracellular lipid accumulation and reduced number of mitochondria. Similar to in vitro condition, the angiogenic capacity of c-kit+ cells was aborted in vivo indicated by reduced NG2 , α-SMA, CD31, and vWF levels. High glucose condition reduces the angio/cardiogenic capacity of cardiac c-kit+ cells in vitro and in vivo. SIGNIFICANCE OF THE STUDY: High glucose condition seen in diabetes mellitus could affect the regenerative potential of cardiac tissue. The current experiment showed that the exposure of murine cardiac progenitor cells (CD117+ cells) to condition containing 30mM glucose could decrease the differentiation properties into endothelial cells, pericytes, and mature cardiomyocytes in vitro and in vivo. Our finding confirmed that the angiogenic/cardiogenic potential cardiac progenitor cells decrease under treatment with high glucose content as seen in the diabetic condition.

In the current experiment, detrimental effects of high glucose condition were investigated on human neuroblastoma cells. Human neuroblastoma cell line SH-SY5Y were exposed to 5, 40, and 70 mM glucose over a period of 72 h. Survival rate and the proliferation of cells were analyzed by MTT and BrdU incorporation assays. Apoptosis was studied by the assays of flow cytometry and PCR array. In order to investigate the trans-differentiation capacity of the cell into mature neurons, we used immunofluorescence imaging to follow NeuN protein level. The transcription level of HSP70 was shown by real-time PCR analysis. MMP-2 and -9 activities were shown by gelatin Zymography. According to data from MTT and BrdU incorporation assay, 70 mM glucose reduced cell viability and proliferation rate as compared to control (5 mM glucose) and cells treated with 40 mM glucose (P < 0.05). Cell exposure to 70 mM glucose had potential to induced apoptosis after 72 h (P < 0.05). Our results also demonstrated the sensitivity of SH-SY5Y cells to detrimental effects of high glucose condition during trans-differentiation into mature neuron-like cells. Real-time PCR analysis confirmed the expression of HSP70 in cells under high content glucose levels, demonstrating the possible cell compensatory response to an insulting condition (pcontrol vs 70 mM group

Abnormal activity of atherosclerotic endothelial cells paving luminal surface of blood vessels has been described in many diseases. It has been reported that natural polyunsaturated fatty acids such as docosahexaenoic acid exert therapeutic effects in atherosclerotic condition. Human umbilical vein endothelial cells were treated with 1mM palmitic acid for 48 hours and exposed to 40μM docosahexaenoic acid for the next 24 hours. Real‐time polymerase chain reaction analysis was used to measure the expression of PTX3, iNOS, and eNOS. The level of nitric oxide was detected by Griess reagent. The transcription level of genes participating in coagulation and blood pressure was studied by polymerase chain reaction array. Docosahexaenoic acid improved the survival rate by reducing apoptosis rate (P < .05). Compared with that of the group given palmitic acid, attenuation of proinflammatory status was indicated by reduced interleukin‐6 (P < .05) and prostaglandin E2 levels. All genes PTX3, iNOS, and eNOS were down‐regulated after being exposed to docosahexaenoic acid. Nitric oxide contents were not changed in cells exposed to docosahexaenoic acid. Polymerase chain reaction array confirmed the reduction of LPA, PDGFβ, ITGA2, SERPINE1, and FGA after exposure to docosahexaenoic acid for 24 hours (P < .05). Docosahexaenoic acid had potential to blunt atherosclerotic changes in the modulation of genes controlling blood coagulation, pressure, and platelet function. Significance of the study The current experiment showed that docosahexaenoic acid could reverse atherosclerotic changes in human endothelial cells induced by palmitic acid. The increased levels of interleukin‐6 and prostaglandin E2 in atherosclerotic cells were returned to near‐to‐normal status. Gene expression analysis showed a reduced activity of genes participating in atherosclerotic endothelial cells treated by docosahexaenoic acid. The expression of genes related to cell clotting activity was also similar to that of normal cells.

This experiment investigated the impact of serum from patients with type 2 diabetes mellitus on the angiogenic behavior of human mesenchymal stem cells in vitro. Changes in the level of Ang-1, Ang-2, cell migration, and trans-differentiation into pericytes and endothelial lineage were monitored after 7 days. The interaction of mesenchymal stem cells with endothelial cells were evaluated using surface plasmon resonance technique. Paracrine restorative effect of diabetic stem cells was tested on pancreatic β cells. Compared to data from FBS and normal serum, diabetic serum reduced the stem cell survival and chemotaxis toward VEGF and SDF-1α (P < 0.05). Diabetic condition were found to decline cell migration rate and the activity of MMP-2 and -9 (P < 0.05). The down-regulation of VEGFR-2 and CXCR-4 was observed with an increase in the level of miR-1-3p and miR-15b-5p at the same time. The paracrine angiogenic potential of diabetic stem cells was disturbed via the changes in the dynamic of Ang-1, Ang-2, and VEGF. Surface plasmon resonance analysis showed that diabetes could induce an aberrant increase in the interaction of stem cells with endothelial cells. After treatment with diabetic serum, the expression of VE-cadherin and NG2 and ability for uptake of Dil-Ac-LDL were reduced (P < 0.01). Conditioned media prepared from diabetic stem cells were unable to decrease fatty acid accumulation in β-cells (P < 0.05). The level of insulin secreted by β-cells was not affected after exposure to supernatant from diabetic or non-diabetic mesenchymal stem cells. Data suggest diabetes could decrease angiogenic and restorative effect of stem cells in vitro. J. Cell. Biochem. 119: 524-535, 2018. © 2017 Wiley Periodicals, Inc.

To date, many studies have been conducted to find out the underlying mechanisms of hyperglycemia-induced complications in diabetes mellitus, attributed to the cellular pathologies of different cells-especially endothelial cells. However, there are still many ambiguities and unresolved issues to be clarified. Here, we investigated the alteration in biophysical and biochemical properties in human umbilical vein endothelial cells exposed to a high-glucose concentration (30mM), comparable to glucose content in type 2 diabetes mellitus, over a course of 120 hours. In addition to a reduction in the rate of cell viability and induction of oxidative stress orchestrated by the high-glucose condition, the dynamic of the fatty acid profile-including polyunsaturated, monounsaturated, and saturated fatty acids-was also altered in favor of saturated fatty acids. Genetic imbalances were also detected at chromosomal level in the cells exposed to the abnormal concentration of glucose after 120 hours. Moreover, the number of tip cells (CD31(+) /CD34(+) ) and in vitro tubulogenesis capability negatively diminished in comparison to parallel control groups. We found that diabetic hyperglycemia was associated with a decrease in the cell-cell tight junction and upregulation in vascular endothelial cadherin and zonula occludens (ZO)-1 molecules after 72 and 120 hours of exposure to the abnormal glucose concentration, which resulted in a profound reduction in transendothelial electrical resistance. The surface plasmon resonance analysis of the human umbilical vein endothelial cells immobilized on gold-coated sensor chips confirmed the loosening of the cell to cell intercellular junction as well as stable attachment of each cell to the basal surface. Our findings highlighted the disturbing effects of a diabetic hyperglycemia on either biochemical or biophysical properties of endothelial cells.

Preserving self-renewal, multipotent capacity, and large-scale expansion of highly functional progenitor cells, including endothelial progenitor cells (EPCs), is a controversial issue. These current limitations, therefore, raise the need of developing promising in vitro conditions for prolonged expansion of EPCs without loss of their stemness feature. In the current study, the possible role of three different natural extracellular substrates, including collagen, gelatin, and fibronectin, on multiple parameters of EPCs such as cell morphology, phenotype, clonogenic, and vasculogenic properties was scrutinized. Next, EPCs from GFP-positive mice were pre-expanded on each of these ECM substrates and then systemically transplanted into sublethaly irradiated mice to analyze the potency of these cells for marrow reconstitution. Our results revealed considerable promise for fibronectin for EPC expansion with maintenance of stemness characteristics, whereas gelatin and collagen matrices directed the cells toward a mature endothelial phenotype. Transplantation of EPCs pre-expanded on fibronectin resulted in widespread distribution and appropriate engraftment to various tissues with habitation in close association with the microvasculature. In addition, fibronectin pre-expanded cells were gradually enriched in the bone marrow after transplantation, resulting in marrow repopulation and hematologic recovery, leading to improved survival of recipient mice whereas gelatin- and collagen-expanded cells failed to reconstitute the bone marrow. This study demonstrated that, cell characteristics of in vitro expanded EPCs are determined by the subjacent matrix. Fibronectin-expanded EPCs are heralded as a source of great promise for bone marrow reconstitution and neo-angiogenesis in therapeutic bone marrow transplantation. J. Cell. Biochem. 117: 1934-1946, 2016. © 2016 Wiley Periodicals, Inc.

Canine mammary tumor is being touted as a model for investigating the human breast cancer. Breast cancer of the both species has similar biological behavior, histopathologic characteristics, and metastatic pattern. In this study, we used the serological proteome analysis to detect autoantigens that elicit a humoral response in dogs with mammary tumor in order to identify serum biomarkers with potential usefulness as diagnostic markers and to better understand molecular mechanisms underlying canine breast cancer development. Protein extract from a cell line was subject to 2DE followed by Western blotting using sera from 15 dogs with mammary tumor and sera from 15 healthy control dogs. Immunoreactive autoantigens were subsequently identified by the MALDI-TOF MS. Four autoantigens, including manganese-superoxide dismutase, triose phosphate isomerase, alpha-enolase, and phosphoglycerate mutase1, with significantly higher immunoreactivity in the tumor samples than in the normal samples were identified as biomarker candidates. Immunohistochemistry and Western blotting revealed higher expression of these biomarkers in the malignant tumors than in the normal or benign tumors. The autoantigens found in this study have been reported to elicit autoantibody response in the human breast cancer, indicating the similarity of breast cancer proteome profile in dogs with that in human beings.