We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2–5.4 μM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics. 相似文献
Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades. 相似文献
The repair of bone fractures is a clinical challenge for patients with impaired healing, such as osteoporosis. Currently, different strategies have been developed to design new biomaterials, enhancing their interactions with biological systems and conducting the cellular behavior in the desired direction to help fracture healing. In the present work, hydroxyapatite-graphene oxide (HA-GO) nanocomposites were produced and the morphological and physicochemical influences of the addition of 0.5 wt%, 1.0 wt% and 1.5 wt% of GO to HA were observed. FEG-SEM and TEM analyses of HA-GO nanocomposites showed HA nanoparticles adhered to the surface of the GO sheets, suggesting an effective method to form nanostructured graphene-based biomaterials. As confirmation, physicochemical analyses by Raman, FTIR and TGA demonstrated a strong affinity between HA and GO, according to the increase of concentration from 0.5 wt% to 1.5 wt% GO in the HA-GO nanocomposites. Also, in order to evaluate the HA-GO nanocomposites behavior under biological microenvironment, in vitro bioactivity and indirect cytotoxicity tests were performed. FEG-SEM analyses confirmed the positive results for the bioactivity properties of HA-GO nanocomposite and indirect cytotoxicity demonstrated that even with a decrease in the hDPSCs viability and proliferation, when increasing to 1.5 wt% of GO concentration, high level of cell viability was exhibited by HA-GO nanocomposites. These biological results suggested the 0.5 wt% HA-GO nanocomposite as a potential bioactive bone graft and a promising biomaterial for bone tissue regeneration, when compared to the pure HA. 相似文献
A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions. 相似文献
Spin-coated chalcostibite CuSbS2 thin films (≈500 nm thick) were fabricated and the influence of the drying temperature on the structural, morphological, optical and thermoelectric properties of the films was investigated. Crystalline phase-pure chalcostibite has been obtained for the films dried at 180 °C and 210 °C, while below 180 °C these films are partially amorphous. Surprisingly, at drying temperature of 240 °C, a CuxS secondary phase appeared. The increase of the drying temperature leads to the increase of the particle size and the decrease of the optical band gap, which is interesting for optoelectronic applications. The highest power factor value was achieved for the film dried at 210 °C, due to the inexistence of secondary phases, which allowed realizing a stable thermoelectric touch sensor with a Vsignal/noise of 5. In addition, this film was tested as a photovoltaic (PV) device and a power conversion efficiency (PCE) of 0.030% with an open-circuit voltage (VOC) of 0.36 V, a short-circuit current density (JSC) of 0.278 mAcm?2 and a fill factor (FF) of 0.27 were obtained. Therefore, this work evidences a pathway toward developing bi-functional devices with simultaneously thermoelectric touch sensor and photovoltaic functions. 相似文献
This research aims to illustrate the potential use of concepts, techniques, and mining process tools to improve the systematic review process. Thus, a review was performed on two online databases (Scopus and ISI Web of Science) from 2012 to 2019. A total of 9649 studies were identified, which were analyzed using probabilistic topic modeling procedures within a machine learning approach. The Latent Dirichlet Allocation method, chosen for modeling, required the following stages: 1) data cleansing, and 2) data modeling into topics for coherence and perplexity analysis. All research was conducted according to the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses in a fully computerized way. The computational literature review is an integral part of a broader literature review process. The results presented met three criteria: (1) literature review for a research area, (2) analysis and classification of journals, and (3) analysis and classification of academic and individual research teams. The contribution of the article is to demonstrate how the publication network is formed in this particular field of research, and how the content of abstracts can be automatically analyzed to provide a set of research topics for quick understanding and application in future projects.