Construction and Characterization of a Novel Fusion Protein MG7-scFv/SEB against Gastric Cancer

Antibody-targeted superantigen has been developed into a new strategy to treat many malignant tumors. In this study, for specific targeting to gastric cancer cell, superantigen SEB (Staphylococcal Enterotoxin B) was genetically fused to the single-chain variable fragment of gastric carcinoma-associated antibody MG7(MG7-scFv) that recognizes the MG7 antigen frequently expressed in gastric cancer cell. The recombinant MG7-scFv/SEB fusion proteins are expressed in E. coli as inclusion bodies, and the purified MG7-scFv/SEB retains high binding affinity with gastric cancer cell SGC-7901 (positive MG7 antigen expression). When incubated with effector cell—peripheral blood mononuclear cells (PBMCs), MG7-scFv/SEB could effectively inhibit the proliferation and induce apoptosis of SGC-7901. After being treated with MG7-scFv/SEB, PBMCs remarkably increased the production of Th1 cytokines (IFN-gamma, IL-2), and slightly increased the production of Th2 cytokines (IL-4, IL-10) in vitro. It was observed that gastric-tumor-bearing rats administrated with MG7-scFv/SEB showed more inflammatory cell infiltration, more significant tumor inhibition, and longer survival time than those of rats treated with SEB or NS (Normal Saline). The data indicated that MG7-scFv/SEB fusion protein could specifically target gastric cancer cell, enhance the activity of T cells and induce tumor cell apoptosis to exert the antitumor effect on gastric cancer

Lepton flavor violating decays lj→liγγl_j\rightarrow l_i \gamma\gamma

In this paper, we study the lepton flavor violating decays of the $l_j\rightarrow l_i \gamma\gamma$ (j=2, 3; i=1, 2) processes under the $U(1)_X$SSM. The $U(1)_X$SSM is the addition of three singlet new Higgs superfields and right-handed neutrinos to the minimal supersymmetric standard model (MSSM). Based on the latest experimental constraints of $l_j\rightarrow l_i \gamma\gamma$, we analyze the effects of different sensitive parameters on the results and made reasonable predictions for future experimental development. Numerical analysis shows that many parameters have a greater or lesser effect on lepton flavor violation(LFV), but the main sensitive parameters and sources leading to LFV are the non-diagonal elements involving the initial and final leptons. This work could provide a basis for the discovery of the existence of new physics (NP)

MicroRNA 506 regulates expression of PPAR alpha in hydroxycamptothecin-resistant human colon cancer cells

AbstractChemotherapeutic drug resistance remains a major obstacle to the successful treatment of colon cancer. Here, we show that 77 differentially expressed miRNAs were identified in SW1116/HCPT versus SW1116, and over-expressed miR-506 in SW1116/HCPT cells was validated. Then it was indicated that PPARα is a common target of miR-506 by using a luciferase reporter assay. Our results also demonstrated that cytotoxic ability of HCPT requires the concomitant presence of PPARα, and that loss of PPARα expression imparts resistance to HCPTs anti-tumor effects. All together, our studies indicate that miR-506 over-expression in established HCPT-resistant colon cancer cell line confers resistance to HCPT by inhibiting PPARα expression, then providing a rationale for the development of miRNA-based strategies for reversing resistance in HCPT-resistant colon cancer cells

Superparamagnetic iron oxide nanoparticles mediated 131I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 ((131)I) against the human vascular endothelial growth factor (hVEGF). METHODS: hVEGF siRNA was labeled with (131)I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. (131)I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of (131)I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment. RESULTS: (131)I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (>80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more (131)I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with (131)I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by (131)I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control. CONCLUSIONS: EMF-guided (131)I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of (131)I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging

Development and validation of molecular markers for characterization of Boehmeria nivea var. nivea and Boehmeria nivea var. tenacissima

<p>Abstract</p> <p>Background</p> <p>The root of <it>Boehmeria </it>spp (ramie) is a hepatoprotective Chinese herbal medicine. Medicinal properties vary between <it>Boehmeria nivea </it>var. <it>nivea </it>and <it>Boehmeria nivea </it>var. <it>tenacissima</it>, which are local species found in Taiwan. As commercial preparations may use either species, there is a need for a rapid and simple assay to identify variants for quality control.</p> <p>Methods</p> <p>Four methods were developed and tested for their applicability in differentiating the two species. These methods were random amplified polymorphic DNA (RAPD); sequence characterized amplified regions (SCAR); single nucleotide polymorphisms (SNP) and cleaved amplified polymorphic sequences (CAPS).</p> <p>Results</p> <p>Three RAPD markers were developed that produced unique bands in <it>B. nivea </it>var. <it>tenacissima </it>and <it>B. nivea </it>var. <it>nivea</it>. Based on sequenced RAPD bands, one SCAR marker was developed that produced a single DNA band in <it>B. nivea </it>var. <it>nivea</it>. Two SNP markers differentiated between <it>B. nivea </it>var. <it>nivea </it>and <it>B. nivea </it>var. <it>tenacissima </it>based on single nucleotide substitutions. A pair of CAPS oligonucleotides was developed by amplifying a 0.55-kb DNA fragment that exhibited species-specific digestion patterns with restriction enzymes <it>Alf </it>III and <it>Nde </it>I. Consistent results were obtained with all the four markers on all tested <it>Boehmeria </it>lines.</p> <p>Conclusion</p> <p>The present study demonstrates the use of the RAPD, SCAR, SNP and CAPS markers for rapid identification of two closely related <it>Boehmeria </it>species.</p

Articles That Use Artificial Intelligence for Ultrasound: A Reader’s Guide

Artificial intelligence (AI) transforms medical images into high-throughput mineable data. Machine learning algorithms, which can be designed for modeling for lesion detection, target segmentation, disease diagnosis, and prognosis prediction, have markedly promoted precision medicine for clinical decision support. There has been a dramatic increase in the number of articles, including articles on ultrasound with AI, published in only a few years. Given the unique properties of ultrasound that differentiate it from other imaging modalities, including real-time scanning, operator-dependence, and multi-modality, readers should pay additional attention to assessing studies that rely on ultrasound AI. This review offers the readers a targeted guide covering critical points that can be used to identify strong and underpowered ultrasound AI studies

Integration of the metabolome and transcriptome reveals the metabolites and genes related to nutritional and medicinal value in Coriandrum sativum

Coriandrum sativum (Coriander) or Chinese parsley is a culinary herb with multiple medicinal effects, which is widely used in cooking and traditional medicine. It is enriched with essential oils and anti-oxidant compounds with unknown significance. To explore the untapped reservoir of Coriander, we studied the transcriptome and metabolic profiles from three developmental stages. Here, we identified 10 tyrosine metabolic pathway-related genes (TMPRGs), six porphyrins and chlorophyll metabolic pathway-related genes (PCMPRGs), and five Vitamin E metabolic pathway-related genes (VEMPRGs). These genes were associated with the early development of Coriander. Our analysis suggests that these pathways are involved in the production of critical phenolic metabolites. Furthermore, we constructed the interaction network between these pathway-related genes and transcription factors (TFs), which supported the regulatory pathways for phenolic metabolites. Interestingly, we identified several nutritional or medicinally relevant metabolites, including 59 phenols, two polyamines, 12 alkaloids, and one terpenoid. The higher concentrations of metabolites were from caffeic acid, agmatine, and its derivatives. We found higher levels of caffeic acid and agmatine at 30 days compared to 60 or 90 days. This study provides evidence to stimulate further investigation of the role of these metabolites in medicinal and nutritional research

Phase-resolved spectral analysis of 4U 1901+03 during its outburst

The high mass X-ray binary 4U 1901+03 was reported to have the pulse profile evolving with the X-ray luminosity and energy during its outburst in February-July 2003: the pulse peak changed from double to single along with the decreasing luminosity. We have carried out a detailed analysis on the contemporary phase-resolved energy spectrum of 4U 1901+03 as observed by Rossi X-ray Timing Explorer (RXTE). We find that, both the continuum and the pulse spectra are phase dependent. The optical depth derived from the pulse spectrum is in general larger than that from the continuum. Fe Ka emission line is only detected in the spectrum of the continuum and is missing in the pulse spectrum. This suggests an origin of Fe emission from the accretion disk but not the surface of the neutron star.Comment: 18 pages, 8 figures, accepted by Ap

Cardiac resynchronization therapy (CRT) with right ventricular sense triggered left ventricular pacing benefits for the hemodynamics compared with standard CRT for chronic congestive heart failure: A cross-over study

Background: The aim of this study was to investigate the effect of cardiac resynchronization therapy (CRT) with right ventricular (RV) sense triggered left ventricular (LV) pacing for chronic heart failure (CHF). Methods: Thirty patients who were eligible for the Class I indication of CRT were enrolled and the informed consents were signed. Left ventricular ejection fraction (LVEF), diastolic mitral flow velocity time integral (VTI), mitral regurgitation flow VTI, and aortic valve flow VTI were measured with GE Vivid 7 (GE Medical, Milwaukee, WI, USA) before and after CRT. The echocardiographic measurements and the average annual costs of the device use were compared. Results: The duration of QRS complex, the length of time used for optimization, and the average annual cost of the device use under RV sense triggered LV pacing were significantly less than that under standard biventricular (BiV) pacing (p &lt; 0.01), while the average battery lifetime was longer. Subgroup analysis showed that LVEF, diastolic mitral flow VTI, and aortic valve flow VTI under RV sense triggered LV pacing were greater than that under standard BiV pacing with right or LV pre-activation. The average battery lifetime was significantly longer and the average annual cost of the device use was less. The mitral regurgitation flow VTI under RV sense triggered LV pacing was less than that under standard BiV pacing with RV pre-activation. Conclusions: RV sense triggered LV provides benefits for CHF patients over standard CRT in terms of maintaining the physiological atrio-ventricular delay of atrio-ventricular node and improving the acute hemodynamic effects