Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

The H1N1 influenza pandemic of 2009 has claimed over 18,000 lives. During this pandemic, development of drug resistance further complicated efforts to control and treat the widespread illness. This research utilizes traditional Chinese medicine Database@Taiwan (TCM Database@Taiwan) to screen for compounds that simultaneously target H1 and N1 to overcome current difficulties with virus mutations. The top three candidates were de novo derivatives of xylopine and rosmaricine. Bioactivity of the de novo derivatives against N1 were validated by multiple machine learning prediction models. Ability of the de novo compounds to maintain CoMFA/CoMSIA contour and form key interactions implied bioactivity within H1 as well. Addition of a pyridinium fragment was critical to form stable interactions in H1 and N1 as supported by molecular dynamics (MD) simulation. Results from MD, hydrophobic interactions, and torsion angles are consistent and support the findings of docking. Multiple anchors and lack of binding to residues prone to mutation suggest that the TCM de novo derivatives may be resistant to drug resistance and are advantageous over conventional H1N1 treatments such as oseltamivir. These results suggest that the TCM de novo derivatives may be suitable candidates of dual-targeting drugs for influenza.National Science Council of Taiwan (NSC 99-2221-E-039-013-)Committee on Chinese Medicine and Pharmacy (CCMP100-RD-030)China Medical University and Asia University (CMU98-TCM)China Medical University and Asia University (CMU99-TCM)China Medical University and Asia University (CMU99-S-02)China Medical University and Asia University (CMU99-ASIA-25)China Medical University and Asia University (CMU99-ASIA-26)China Medical University and Asia University (CMU99-ASIA-27)China Medical University and Asia University (CMU99-ASIA-28)Taiwan Department of Health. Clinical Trial and Research Center of Excellence (DOH100-TD-B-111-004)Taiwan Department of Health. Cancer Research Center of Excellence (DOH100-TD-C-111-005

Synthesis and Biological Evaluation of Phenanthrenes as Cytotoxic Agents with Pharmacophore Modeling and ChemGPS-NP Prediction as Topo II Inhibitors

In a structure-activity relationship (SAR) study, 3-methoxy-1,4-phenanthrenequinones, calanquinone A (6a), denbinobin (6b), 5-OAc-calanquinone A (7a) and 5-OAc-denbinobin (7b), have significantly promising cytotoxicity against various human cancer cell lines (IC50 0.08–1.66 µg/mL). Moreover, we also established a superior pharmacophore model for cytotoxicity (r = 0.931) containing three hydrogen bond acceptors (HBA1, HBA2 and HBA3) and one hydrophobic feature (HYD) against MCF-7 breast cancer cell line. The pharmacophore model indicates that HBA3 is an essential feature for the oxygen atom of 5-OH in 6a–b and for the carbonyl group of 5-OCOCH3 in 7a–b, important for their cytotoxic properties. The SAR for moderately active 5a–b (5-OCH3), and highly active 6a–b and 7a–b, are also elaborated in a spatial aspect model. Further rational design and synthesis of new cytotoxic phenanthrene analogs can be implemented via this model. Additionally, employing a ChemGPS-NP based model for cytotoxicity mode of action (MOA) provides support for a preliminary classification of compounds 6a–b as topoisomerase II inhibitors

The Advancement of Biomaterials in Regulating Stem Cell Fate.

Stem cells are well-known to have prominent roles in tissue engineering applications. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can differentiate into every cell type in the body while adult stem cells such as mesenchymal stem cells (MSCs) can be isolated from various sources. Nevertheless, an utmost limitation in harnessing stem cells for tissue engineering is the supply of cells. The advances in biomaterial technology allows the establishment of ex vivo expansion systems to overcome this bottleneck. The progress of various scaffold fabrication could direct stem cell fate decisions including cell proliferation and differentiation into specific lineages in vitro. Stem cell biology and biomaterial technology promote synergistic effect on stem cell-based regenerative therapies. Therefore, understanding the interaction of stem cell and biomaterials would allow the designation of new biomaterials for future clinical therapeutic applications for tissue regeneration. This review focuses mainly on the advances of natural and synthetic biomaterials in regulating stem cell fate decisions. We have also briefly discussed how biological and biophysical properties of biomaterials including wettability, chemical functionality, biodegradability and stiffness play their roles

Ethnic and geographic diversity of stone disease

Objectives. To ascertain diversity or similarity in stone prevention and problems among different countries around the world.Methods. Urolithiasis research groups from 10 countries completed a questionnaire.Results. Cost of extracorporeal shock wave lithotripsy (ESWL) was considerably greater than that of drugs in four countries, and equivalent in remaining countries. Stone composition was similar among different countries. Certain urinary risk factors were associated with particular countries, probably from dietary indiscretions. ESWL was used in the majority of patients and open surgery in a minority of patients, except in one country. Medical diagnostic evaluation was used in the majority of patients except in one country. Drug treatment was nonselective, and provided to a minority of recurrent stone-formers.Conclusions. There is considerable similarity in stone presentations and problems throughout the world. the diversity is likely to be due to nutritional-environmental and socio-political-economic factors. (C) 1997, Elsevier Science Inc. All rights reserved.CASE WESTERN RESERVE UNIV,DEPT UROL,CLEVELAND,OH 44106DUKE UNIV,MED CTR,DIV UROL,DURHAM,NCLINKOPING UNIV HOSP,DEPT UROL,S-58185 LINKOPING,SWEDENUNIV HOSP BERN,POLICLIN MED,CH-3010 BERN,SWITZERLANDSECUR FORCES HOSP,RIYADH,SAUDI ARABIAMED COLL HOSP TRIVANDRUM,TRIVANDRUM,KERALA,INDIADONG A UNIV HOSP,DEPT UROL,PUSAN,SOUTH KOREASHIN KONG WU HO SU MEM HOSP,DIV UROL,TAIPEI,TAIWANWAKAYAMA MED COLL,DEPT UROL,WAKAYAMA 640,JAPANWINNIPEG HLTH SCI CTR,DEPT UROL,WINNIPEG,MB,CANADAUniversidade Federal de São Paulo,São Paulo,BRAZILUniversidade Federal de São Paulo,São Paulo,BRAZILWeb of Scienc