The trans-differentiation promotion of parietal epithelial cells by magnesium isoglycyrrhizinate to improve podocyte injury induced by high fructose consumption.

Background: Podocytes have limited proliferative capacity, which leads to irreversible glomerular injury in diverse kidney diseases. Magnesium isoglycyrrhizinate (MgIG), a hepatoprotective agent in clinic, has been reported to improve glomerular podocyte injury. However, the underlying mechanism of MgIG in ameliorating podocyte injury remains unclear.

SLC27A5 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by downregulating glutathione reductase.

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), shows a favorable anti-tumor effect while resistance is a barrier impeding patients from benefiting from it. Thus, more efforts are needed to lift this restriction. Herein, we first find that solute carrier family 27 member 5 (SLC27A5/FATP5), an enzyme involved in the metabolism of fatty acid and bile acid, is downregulated in sorafenib-resistant HCC.

Designing a nanoparticle-containing polymeric substrate for detecting cancer cells by computer simulations.

Efficient and accurate detection of cancer cells (from normal cells) is of great importance in cancer diagnosis and prognosis. In this work, we design a new type of polymeric substrate containing nanoparticles for detecting cancers by the dissipative particle dynamics (DPD) simulation. It is found that the cancer cells and the normal cells can be indeed distinguished since the uptake number of nanoparticles from the substrate is different.

Ion transport through a nanoporous CN membrane: the effect of electric field and layer number.

Ion transport through a two-dimensional membrane with nanopores plays an important role in many scientific and technical applications (, water desalination, ion separation and nanofiltration). Although there have been many two-dimensional membranes for these applications, the problem of how to controllably fabricate nanopores with proper shape and size still remains challenging. In the present work, the transport of ions through a CN membrane with intrinsically regular and uniformly distributed nanopores is investigated using all-atom molecular dynamic simulations.

Discovery of Potent and Selective Inhibitors of Cdc2-Like Kinase 1 (CLK1) as a New Class of Autophagy Inducers.

Autophagy inducers represent new promising agents for the treatment of a wide range of medical illnesses. However, safe autophagy inducers for clinical applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently found to efficiently induce autophagy.

Engineering P450 Peroxygenase to Catalyze Highly Enantioselective Epoxidation of cis-β-Methylstyrenes.

P450 119 peroxygenase and its site-directed mutants are discovered to catalyze the enantioselective epoxidation of methyl-substituted styrenes. Two new site-directed P450 119 mutants, namely T213Y and T213M, which were designed to improve the enantioselectivity and activity for the epoxidation of styrene and its methyl substituted derivatives, were studied. The T213M mutant is found to be the first engineered P450 peroxygenase that shows highly enantioselective epoxidation of cis-β-methylstyrenes, with up to 91 % ee.

Design, Synthesis, and Biological Evaluation of 1-Benzyl-1H-pyrazole Derivatives as Receptor Interacting Protein 1 Kinase Inhibitors.

Receptor interacting protein 1 (RIP1) kinase plays an important role in necroptosis, and inhibitors of the RIP1 kinase are thought to have a potential therapeutic value in the treatment of diseases related to necrosis. Herein, we report the structural optimization of a RIP1 kinase inhibitor, 1-(2,4-dichlorobenzyl)-3-nitro-1H-pyrazole (1a). A number of 1-benzyl-1H-pyrazole derivatives were synthesized and structure-activity relationship (SAR) analysis led to the discovery of a potent compound, 4b, which showed a Kd value of 0.

The adjuvant effects of high-molecule-weight polysaccharides purified from Antrodia cinnamomea on dendritic cell function and DNA vaccines.

The biological activity of the edible basidiomycete Antrodia cinnamomea (AC) has been studied extensively. Many effects, such as anti-cancer, anti-inflammatory, and antioxidant activities, have been reported from either crude extracts or compounds isolated from AC. However, research addressing the function of AC in enhancing immunity is rare.

A prediction model of drug-induced ototoxicity developed by an optimal support vector machine (SVM) method.

Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to be considered in drug discovery. Nevertheless, current experimental methods used to evaluate drug-induced ototoxicity are often time-consuming and expensive, indicating that they are not suitable for a large-scale evaluation of drug-induced ototoxicity in the early stage of drug discovery. We thus, in this investigation, established an effective computational prediction model of drug-induced ototoxicity using an optimal support vector machine (SVM) method, GA-CG-SVM.

Phloroglucinols with prooxidant activity from Garcinia subelliptica.

A new phloroglucinol, garcinielliptone HF ( 1), possessing an unprecedented skeleton, and the tautomeric pair of garcinielliptone FC ( 2/ 2a) were isolated from the heartwood and pericarp of Garcinia subelliptica, respectively. Their structures, including relative configurations, were elucidated by means of spectroscopic methods. The ability of compounds 1 and 2/ 2a to induce DNA-cleavage activity was examined using supercoiled plasmid pBR322 DNA.

DNA strand-scission by phloroglucinols and lignans from heartwood of Garcinia subelliptica Merr. and Justicia plants.

Five 2,4,6-prenylated phloroglucinols, garcinielliptones HA (1), HB (2), HC (3), HD (4) and HE (5), were isolated from the heartwood of Garcinia subelliptica Merr. Their structures, including relative configurations, were elucidated by means of spectroscopic data analysis. The ability of phloroglucinols, 1-5 and lignans, tuberculatin (8), justicidin A (9), procumbenoside A (10) and ciliatosides A (11) and B (12), isolated from Justicia ciliata and Justicia procumbens, to induce DNA-cleavage activity was examined using pBR322, a supercoiled, covalently closed circular DNA, and it was analyzed by agarose gel electrophoresis.

Antiplatelet prenylflavonoids from Artocarpus communis.

Four flavonoids, dihydroartomunoxanthone (1), artomunoisoxanthone (2), cyclocomunomethonol (3) and artomunoflavanone (4), together with three known compounds, artochamins B (5), D and artocommunol CC (6) were isolated from the cortex of the roots of Artocarpus communis. The structures of 1-4 were determined by spectroscopic methods. The antiplatelet effects of the flavonoids, 1-3, 5 and 6 on human platelet-rich plasma (PRP) were evaluated.

Cytotoxic prenylflavonoids from Artocarpus elasticus.

Five new prenylated flavonoids, artelastoheterol (1), artelasticinol (2), cycloartelastoxanthone (3), artelastoxanthone (4), and cycloartelastoxanthendiol (5), along with five known compounds, were isolated from the root bark of Artocarpus elasticus. The structures of 1-5 were elucidated by spectroscopic methods and through comparison with data reported in the literature. The previously known compound artonol A (6) exhibited cytotoxic activity against the A549 human cancer cell line, with an ED50 value of 1.