An iron oxide nanoworm hybrid on an interdigitated microelectrode silica surface to detect abdominal aortic aneurysms.

An abdominal aortic aneurysm (AAA) is abnormal swelling in the abdominal aorta and a prevalent life-threatening disease. This research introduces a new interdigitated microelectrode (IDME)-sensing surface modified by iron oxide nanoworms (IONWs) for detecting the AAA biomarker insulin-like growth factor-1 (IGF1). A sandwich pattern was formulated with the IGF1 aptamer and IGFBP1 (IGF binding protein-1) on the IONW-constructed IDME hybrid to identify IGF1. The surface morphology of the IONWs revealed a uniform distribution of worm-like structures (80-100 nm) as confirmed by FESEM and FETEM analyses. Further, the presence of the major elements, Fe and O, was confirmed by EDX and XPS studies. The crystal planes that appeared in the IONW reflect cubic magnetite. IONW-modified IDME attained a limit of detection for IGF1 of 1 fM (3σ) with an aptamer-IGF1-IGFBP1 sandwich. This sandwich with IGFBP1 enhanced the current level at all concentrations of IGF1 and displayed linearity in the range 1 fM to 100 pM with a determination coefficient of R2 = 0.9373 [y = 3.38221x - 4.79]. Control experiments with complementary aptamer sequences, IGF2 and IGFBP3 did not show notable signal changes, indicating the specific detection of IGF1. This IONW constructed electrode helps to achieve the detection of low amounts of IGF1 and diagnose AAA at the stage prior to rupture.

Involvement of orbit in maxillofacial fractures: "Evaluation of its spectrum, characteristics, and treatment in 200 patients"-Prospective study.

BACKGROUND: To evaluate the orbital involvement epidemiology in facial fractures, the clinical distribution and effects of orbital involvement in these patients, the frequency and nature of treatment procedures performed for these involvements, and the immediate- and intermediate-term effects of these treatment procedures. METHODS: Two hundred patients with hard tissue maxillofacial injuries were included in this study. Clinical examination was performed in-depth. Images were taken to determine and confirm clinical observations and to finalize treatment modality. Orbital involvement in patients was noted as present or absent. The clinical effects and features in postoperative imaging studies were noted until 3 months after trauma in each patient. RESULTS: Out of 200 patients, about one-third patients (58;29%) had orbital involvement and out of which 49 were males. Regarding clinical-radiological signs in orbit involved fractures, the incidences were variable, that is, periorbital ecchymosis (77.6%), periorbital edema (74.1%), subconjunctival hemorrhage (67.2%), palpable step/crepitus in orbital rim (62.1%), infraorbital nerve paresthesia (46.6%), restricted globe movement (5.2%), orbital rim discontinuity/step (72.4%), maxillary sinuses (51.7%), orbital wall/floor/roof rupture (55.2%), and infraorbital foramen involvement (36.2%). Palpable step/crepitus in orbital rim was recovered remarkably earlier in patients of open reduction internal fixation (ORIF) group, and features of restricted globe movements, orbital rim discontinuity/step, orbital wall/floor/roof rupture, and infraorbital foramen involvement in patients were recovered immediately after open reduction and internal fixation treatment. CONCLUSION: Early repair of the maxillofacial injuries with orbital involvement has better functional and esthetic outcome.

Induced Tamoxifen Resistance is Mediated by Increased Methylation of E-Cadherin in Estrogen Receptor-Expressing Breast Cancer Cells.

Estrogen receptor-positive breast cancers are treated with tamoxifen, a drug that competitively inhibits the binding of estrogen to its receptor. Resistance to tamoxifen is a major hurdle in effective management of target breast cancer patient population. A number of dynamic changes within the tumor microenvironment, including the phenomenon of epithelial to mesenchymal transition (EMT), determine the response to endocrine therapy. EMT is marked by silencing or suppression of epithelial marker, E-Cadherin and we found significantly down-regulated E-Cadherin, among other epithelial markers, and a significantly up-regulated mesenchymal marker, Twist, among other mesenchymal markers, in a model system that comprised of tamoxifen sensitive MCF-7 cells and their tamoxifen-resistant counterparts, MCF-7-TAM, developed by chronic and escalating exposure of parental cells to tamoxifen. Further, E-cadherin, but not Twist, was differentially expressed in MCF-7-TAM cells because of differential methylation. Treatment with demethylating agent 5-azacytidine increased the expression of E-cadherin thus verifying a role of methylation in its silencing and, moreover, 5-azacytidine treatment also re-sensitized MCF-7-TAM cells to tamoxifen, as evaluated by assays for viability, apoptosis and migration potential. The 5-azacytidine effects were similar to effects of E-cadherin overexpression in MCF-7-TAM cells. This work describes novel mechanism of E-cadherin downregulation in tamoxifen resistant breast cancer cells. Further studies are needed to exploit this information for betterment of breast cancer therapy.

Biosynthesis of size-controlled gold nanoparticles using M. lucida leaf extract and their penetration studies on human skin for plastic surgery applications.

Recently, majority of the studies were focusing on the nanoparticles (NPs) and their abilities of penetrating Stratum Corneum (SC), as they can be prominently utilized in the plastic surgeries. In the current work, we demonstrated the penetrating abilities of gold NPs (AuNPs) through anthropological skin with diameters of 10 and 15 nm, varying in sizes, with the help of Multiphoton Microscopy. In addition, we also demonstrated a rapid facile environment friendly process of synthesizing AuNPs of adjustable sizes with the help of aqueous M. lucida leaf extract. Surface plasmon resonance was performed to confirm the synthesis of AuNPs at 530 nm with the help of UV-vis spectrophotometer. By differentiating the quantities of M. lucida leaf aqueous extracts, we studied the reduction time, morphological differences and size of the AuNPs. By performing Fourier Transformation Infrared Spectroscopy (FTIR), UV-vis spectroscopy, Transmission Electron Microscopy (TEM), Powder X-ray Diffraction (XRD), Energy Dispersive X-ray Spectroscopy (EDAX) and Selected Area Electron Diffraction (SAED), we characterized the fabricated AuNPs. The further aggregation and growth of AuNPs was protected by the polyphenols in the oxidised form by having a coordination with the surface of AuNPs. Moreover, the experiments of skin penetration showed an effort to deeply examine the factors leading to the penetration of particles into the human skin. These responses indicate that NPs at the determined size ranges penetrate the SC in the same pattern of the drug molecules, mostly by the intercellular paths. These responses attained were essential for developing a unique transdermal transporter as well as for understanding the basic interaction of skin-NPs for the application of plastic surgeries.

Risk factors and therapies in vascular diseases: An umbrella review of updated systematic reviews and meta-analyses.

Aberrant blood vessel functioning and systemic circulation are key causes for vascular disorders; cardiovascular, cerebrovascular, renal artery stenosis, and peripheral artery diseases. Epidemiological and basic science evidence supported genetic reasons, compounded by obesity, hypercholesterolemia, hypertension, diabetes, and smoking as risk factors. This is an umbrella review of risk factors and therapies in vascular disorders, exploring systematic reviews and meta-analyses studies in PubMed, Cochrane, Embase, and Central published in January 2000-May 2018. We made qualitative eligibility gradation of the articles based on inclusion criteria, and independently extracted descriptive and methodologic data to compile their outcomes. We considered 95% confidence interval and the between-study heterogeneity, designated by I 2 . Overall, we extracted 217 studies of impressive quality and at low risk of bias, including 124, 30, 23, 32, and 8, respectively, for the search terms "cardiovascular," "renal," "cerebral," and "limb ischemia" each in combination with "risk factors" and "therapeutics." Our search on genome-wide analyses revealed genes associated with HDL-cholesterol, matrix metalloproteases, angiogenesis, notch3, renin-angiotensin, apolipoprotein E, insulin, and cytokine levels as critical participants in the pathogenesis of vascular diseases. Hypertension and endothelial growth factor-linked polymorphisms were found to contribute to vascular damage. The studies reinforced that lifestyle and dietary patterns influenced susceptibility of circulatory system diseases. Additionally, endovascular medicines, surgical vascularization, angioplasty, and renal artery stenting appeared as major therapeutic approaches in vascular patients. Altogether, our review offers up-to-date information on pathophysiology of vascular diseases and provides insight into existing research, clinical management and clinical gaps in the field.

Cardioprotection and improvement in endothelial-dependent vasodilation during late-phase of whole body hypoxic preconditioning in spontaneously hypertensive rats via VEGF and endothelin-1.

The present study was designed to investigate the effect of late phase of whole body hypoxic preconditioning on endothelial-dependent vasorelaxation and cardioprotection from ischemia-reperfusion injury in spontaneously hypertensive rats (SHR). Hypoxic preconditioning was performed by subjecting rats to four episodes of alternate exposure to low O2 (8%) and normal air O2 of 10 min each. After 24 h, the mesenteric arteries and hearts were isolated to determine the vascular function and cardioprotection from ischemia-reperfusion (I/R) injury on the Langendorff apparatus. There was a significant impairment in acetylcholine-induced relaxation in norepinephrine precontracted arteries (endothelium-dependent function) and increase in I/R-induced myocardial injury in SHR in comparison to Wistar Kyoto rats (WKY). However, hypoxic preconditioning significantly restored endothelium-dependent relaxation in SHR and attenuated I/R injury in both SHR and WKY. Hypoxic preconditioning also led to an increase in the levels of endothelin-1 (not endothelin-2 or -3), vascular endothelial growth factor-A (VEGF-A) and HIF-1α levels. Pretreatment with bevacizumab (anti-VEGF-A) and bosentan (endothelin receptor blocker) significantly attenuated hypoxic preconditioning-induced restoration of endothelium-dependent relaxation and cardioprotection from I/R injury. These interventions also attenuated the levels of VEGF-A and HIF-1α without modulating the endothelin-1 levels. It may be concluded that an increase in the endothelin-1 levels with a subsequent increase in HIF-1α and VEGF expression may possibly contribute in improving endothelium-dependent vasorelaxation and protecting hearts from I/R injury in SHR during late phase of whole body hypoxic preconditioning.

Knockdown of SRPX2 inhibits the proliferation, migration, and invasion of prostate cancer cells through the PI3K/Akt/mTOR signaling pathway.

Sushi repeat-containing protein X-linked 2 (SRPX2), a novel chondroitin sulfate proteoglycan, is reported to play a critical role in tumorigenesis. However, the expression and functional role of SRPX2 in prostate cancer have not been defined. Thus, the aim of this study was to investigate the expression and functional role of SRPX2 in human prostate cancer. Our results showed that the expression of SRPX2 was obviously increased in human prostate cancer tissues and cell lines. In addition, knockdown of SRPX2 inhibited the proliferation, migration, and invasion of prostate cancer cells, as well as prevented the epithelial-mesenchymal transition process in prostate cancer cells. Mechanically, knockdown of SRPX2 efficiently inhibited the activation of PI3K/Akt/mTOR pathway in prostate cancer cells. Taken together, these data demonstrated that knockdown of SRPX2 inhibits the proliferation and metastasis in human prostate cancer cells, partly through the PI3K/Akt/mTOR signaling pathway. Thus, SRPX2 may be a novel therapeutic target for the treatment of prostate cancer.

Pokemon and MEF2D co-operationally promote invasion of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most deadly human malignancy, and frequent invasion and metastasis is closely associated with its poor prognosis. However, the molecular mechanism underlying HCC invasion is still not completely elucidated. Pokemon is a well-established oncogene for HCC growth, but its contribution to HCC invasion has not been studied yet. In this paper, Pokemon was found to be overexpressed in MHCC-97H HCC cell line, which possesses higher invasiveness. Downregulation of Pokemon abolished the invasion of MHCC-97H HCC cell lines. Pokemon overexpression was able to enhance the invasion of MHCC-97L cells with lower invasiveness. MEF2D, an oncogene promoting the invasion of HCC cells, was further detected to be upregulated and downregulated when Pokemon was overexpressed and silenced, respectively. Online database analysis indicated that one Pokemon recognition site was located within the promoter of MEF2D. Chromatin co-precipitation, luciferase, and qPCR assays all proved that Pokemon can promote the expression of MEF2D in HCC cells. Restoration of MEF2D expression can prevent the impaired invasion of HCC cells with Pokemon silencing, while suppression of MEF2D abolished the effect of Pokemon overexpression on HCC invasion. More interestingly, MEF2D was also found to increase the transcription of Pokemon by binding myocyte enhancer factor 2 (MEF2) sites within its promoter region, implying an auto-regulatory circuit consisting of these two oncogenes that can promote HCC invasion. Our findings can contribute to the understanding of molecular mechanism underlying HCC invasion, and provided evidence that targeting this molecular loop may be a promising strategy for anti-invasion therapy.

AGR2 expression is regulated by HIF-1 and contributes to growth and angiogenesis of glioblastoma.

Glioblastoma multiforme (GBM) tumors are the most common type of brain tumors characterized by extensive angiogenesis that is mostly orchestrated by tumor hypoxia. The hypoxia induced factor-1 (HIF-1) transcriptional complex is the "master control switch" for hypoxia. Dysregulation of anterior gradient protein 2 (AGR2) expression is associated with tumor growth and metastasis. Whether AGR2 is a hypoxia-responsive factor and affects tumor progression via angiogenesis remains unknown. Here, we show that GBM cell lines, U87 and LN18, exhibited enhanced hypoxic responses compared with control normal human astrocytes, and a corresponding HIF-1-dependent increase in AGR2 mRNA and protein. Recombinant AGR2 and conditioned medium from GBM cells induced human umbilical vein endothelial cell (HUVEC) migration and tube formation, which were abrogated by anti-AGR2 neutralizing antibodies. Expression of the HIF-1α oxygen-dependent degradation domain mutant in cells resulted in elevated AGR2 levels and an increased ability to induce HUVEC migration and tube formation in vitro and enhanced growth and vascularity of tumor xenografts in vivo, which were prevented by AGR2 knockdown. Taken together, these results indicate that AGR2 expression is regulated by HIF-1 and plays an important role in control of glioblastoma growth and vascularity. Our findings suggest that inhibiting AGR2 may represent a new therapeutic target for anti-angiogenic cancer treatment.