Louis Pasteur, molecular dissymmetry, therapeutic chemistry and neuropharmacology.

Louis Pasteur is celebrated as the founding father of microbiology. But he was a chemist by training and discovered molecular dissymmetry experimentally. All his life, his constant preoccupation will be to apply the method and strategies of the fundamental sciences to living processes, "from the molecule to the brain". His fundamental aim will be, beyond the biology of microbes, the chemistry of life, a disposition which signs the originality of his work. More unexpectedly, Pasteur was at the origin of therapeutic chemistry-which his successors, and especially Daniel Bovet, brilliantly illustrated at the Pasteur Institute and which they would pursue with the pharmacology of the nervous system or "neuropharmacology".

Louis Pasteur est célébré comme le père fondateur de la microbiologie. Mais Il est chimiste de formation et découvre expérimentalement la dissymétrie moléculaire. Toute sa vie, sa constante préoccupation sera d'appliquer la méthode et les stratégies des sciences fondamentales aux processus vivants, « de la molécule au cerveau ¼. Sa visée fondamentale sera, au-delà de la biologie des microbes, la chimie de la vie, une disposition qui signe l'originalité de son œuvre. De manière plus inattendue, Pasteur se trouve à l'origine de la chimie thérapeutique ­ que ses successeurs, et tout particulièrement Daniel Bovet ­ ont brillamment illustrés à l'Institut Pasteur et qu'ils poursuivront avec la pharmacologie du système nerveux ou « neuropharmacologie ¼.

Enhancement of Photodynamic Cancer Therapy by Physical and Chemical Factors.

The viable use of photodynamic therapy (PDT) in cancer therapy has never been fully realized because of its undesirable effects on healthy tissues. Herein we summarize some physicochemical factors that can make PDT a more viable and effective option to provide future oncological patients with better-quality treatment options. These physicochemical factors include light sources, photosensitizer (PS) carriers, microwaves, electric fields, magnetic fields, and ultrasound. This Review is meant to provide current information pertaining to PDT use, including a discussion of in vitro and in vivo studies. Emphasis is placed on the physicochemical factors and their potential benefits in overcoming the difficulty in transitioning PDT into the medical field. Many advanced techniques, such as employing X-rays as a light source, using nanoparticle-loaded stem cells and bacteriophage bio-nanowires as a photosensitizer carrier, as well as integration with immunotherapy, are among the future directions.

The Molecular Basis of Evolution and Disease: A Cold War Alliance.

This paper extends previous arguments against the assumption that the study of variation at the molecular level was instigated with a view to solving an internal conflict between the balance and classical schools of population genetics. It does so by focusing on the intersection of basic research in protein chemistry and the molecular approach to disease with the enactment of global health campaigns during the Cold War period. The paper connects advances in research on protein structure and function as reflected in Christian Anfinsen's The molecular basis of evolution, with a political reading of Emilé Zuckerkandl and Linus Pauling's identification of molecular disease and evolution. Beyond atomic fallout, these advances constituted a rationale for the promotion of genetic surveys of human populations in the Third World, in connection with international health programs. Light is shed not only on the experimental roots of the molecular challenge but on the broader geopolitical context where the rising role of biomedicine and public health (particularly the malaria eradication campaigns) had an impact on evolutionary biology.

Training effect of case-based learning on post competency of medical students in the teaching of medical chemistry / 中华医学教育探索杂志

Objective To investigate the training effect of the case-based learning (CBL) teaching method on post competency of medical students. Methods Four classes of students majoring in nursing in China Medical University were enrolled and divided into experimental group and control group, with two classes in each group. In the teaching of medical chemistry, the CBL teaching method was adopted for the experimental group and the traditional teaching method was adopted for the control group, with the same teacher and teaching materials. Questionnaire survey and final examination were performed to assess the effect of the CBL teaching method on post competency of medical students, and SPSS 20.0 software was used for data analysis. Results The results of the questionnaire survey showed that the experimental group had better assessment indices of post competency. The results of the final examination showed that the experimental group had a significantly higher mean score of medical chemistry than the control group [(73.5 ±10.3) vs. (68.1 ±9.1)]. Conclusion The application of the CBL teaching method in medical chemistry can effectively improve the learning outcomes of medical students and train their post competency, and therefore, it holds promise for application in the teaching of basic medicine.

Discovery of a Highly Potent and Broadly Effective Epidermal Growth Factor Receptor and HER2 Exon 20 Insertion Mutant Inhibitor.

Exon 20 insertion (Ex20Ins) mutations are the third most prevalent epidermal growth factor receptor (EGFR) activating mutation and the most prevalent HER2 mutation in non-small cell lung cancer (NSCLC). Novel therapeutics for the patients with Ex20Ins mutations are urgently needed, due to their poor responses to the currently approved EGFR and HER2 inhibitors. Here we report the discovery of highly potent and broadly effective EGFR and HER2 Ex20Ins mutant inhibitors. The co-crystal structure of compound 1 b in complex with wild type EGFR clearly revealed an additional hydrophobic interaction of 4-fluorobenzene ring within a deep hydrophobic pocket, which has not been widely exploited in the development of EGFR and HER2 inhibitors. As compared with afatinib, compound 1 a exhibited superior inhibition of proliferation and signaling pathways in Ba/F3 cells harboring either EGFR or HER2 Ex20Ins mutations, and in the EGFR P772_H773insPNP patient-derived lung cancer cell line DFCI127. Our study identifies promising strategies for development of EGFR and HER2 Ex20Ins mutant inhibitors.

Reform on flipped classroom teaching in medical chemistry experiment course in the context of"internet" / 中华医学教育探索杂志

Objective To investigate the effect of flipped classroom based on WeChat and mi-crolecture in medical chemistry experiment course in the context of "internet". Methods The classes were randomly divided into 2 groups, experimental group (flipped classroom teaching, n=97) and the control group (traditional teaching, n=98). Comparison of the chemistry experiment test results were performed with the use of t test between the two teaching groups at the end of the semester to evaluate the experimental teaching method. All statistical processing and analyses were performed with SPSS software (version 12.0). Results The chemistry experiment test score of the experimental group was higher than that of the control group [(77.84±8.22) vs. (73.43±10.14), t=3.341, P=0.008), and the difference was statistically significant. The results of the questionnaire showed that the students in the experimental group generally consider that flipped classroom teaching is better than the traditional teaching in terms of the cultivation of comprehen-sive quality and the teaching effect. Conclusion In the context of "internet", flipped classroom teaching with WeChat microlecture can better mobilize the enthusiasm of students to learn and participate in medical chemistry experiment course, which has been welcomed by students and further suggest good application prospects.

A Synthetic Loop Replacement Peptide That Blocks Canonical NF-κB Signaling.

Aberrant canonical NF-κB signaling is implicated in diseases from autoimmune disorders to cancer. A major therapeutic challenge is the need for selective inhibition of the canonical pathway without impacting the many non-canonical NF-κB functions. Here we show that a selective peptide-based inhibitor of canonical NF-κB signaling, in which a hydrogen bond in the NBD peptide is synthetically replaced by a non-labile bond, shows an about 10-fold increased potency relative to the original inhibitor. Not only is this molecule, NBD2, a powerful tool for dissection of canonical NF-κB signaling in disease models and healthy tissues, the success of the synthetic loop replacement suggests that the general strategy could be useful for discovering modulators of the many protein-protein interactions mediated by such structures.

Computational Methods Applied to Rational Drug Design.

Due to the synergic relationship between medical chemistry, bioinformatics and molecular simulation, the development of new accurate computational tools for small molecules drug design has been rising over the last years. The main result is the increased number of publications where computational techniques such as molecular docking, de novo design as well as virtual screening have been used to estimate the binding mode, site and energy of novel small molecules. In this work I review some tools, which enable the study of biological systems at the atomistic level, providing relevant information and thereby, enhancing the process of rational drug design.

To Stress Innovation and Improve the Quality and Effect of Medical Chemistry Experiment Teaching / 中华医学教育探索杂志

Medical chemistry is one of the important basic medicines.Faced with the rapid development of education,Medical chemical education reform or innovation should also keep vigorous.In this paper,we discuss how to innovate and improve the quality and effect of experiment in the process of medical chemistry experiment and lay a solid foundation for continued study.

Application of PBL in medical chemistry experimental teaching / 中华医学教育探索杂志

Applying combined PBL and traditional teaching method to medical chemistry experimental teaching.Questionnaire and course examination were used to evaluate teaching ef-fect.The conclusion was that PBL teaching method was more helpful and effective than that of single traditional teaching method.

Analysis and reflections on the medical chemistry examination results of nursing students / 中华医学教育探索杂志

Because of the different high school background of liberal arts or science,the students showed significant differences in the examination of medical chemistry. In view of this situation,the article tried to find the way of fully mobilizing the enthusiasm of the students and to achieve the desired goal of teaching and learning performance.

The Practice and Exploration of Teaching Reform on Medical Chemistry Experiment / 中华医学教育探索杂志

A series of reforms on the teaching of medical chemistry experiment has been carried out to arouse students' interest in medical chemistry experiment study and improve the quality of instruction,which includes the content of course,the teaching method and the inspection method.Good results have been achieved in the aspect of development of students' comprehensive quality,which lays a good foundation for the study of other courses.

Exploration for teaching reformation of medical chemistry in the nursing major / 中华医学教育探索杂志

A series of reform on the teaching of medical chemistry has been carried out to improve the quality of instruction,which includes the goal of instruction,the content of course and the teaching method.Good results have been achieved.