Rational drug repurposing for alzheimer's treatment using in-silico ligand and structure-based approaches

Abstract Alzheimer's disease is a devastating neurodegenerative disorder characterized by memory loss and cognitive decline. New AD treatments are essential, and drug repositioning is a promising approach. In this study, we combined ligand-based and structure-based approaches to identify potential candidates among FDA-approved drugs for AD treatment. We used the human acetylcholinesterase receptor structure (PDB ID: 4EY7) and applied Rapid Overlay of Chemical Structures and Swiss Similarity for ligand-based screening.Computational shape-based screening revealed 20 out of 760 FDA approved drugs with promising structural similarity to Donepezil, an AD treatment AChE inhibitor and query molecule. The screened hits were further analyzed using docking analysis with Autodock Vina and Schrodinger glide. Predicted binding affinities of hits to AChE receptor guided prioritization of potential drug candidates. Doxazosin, Oxypertine, Cyclopenthiazide, Mestranol, and Terazosin exhibited favorable properties in shape similarity, docking energy, and molecular dynamics stability.Molecular dynamics simulations confirmed the stability of the complexes over 100 ns. Binding free energy analysis using MM-GBSA indicated favourable binding energies for the selected drugs. ADME, formulation studies offered insights into therapeutic applications and predicted toxicity.This comprehensive computational approach identified potential FDA-approved drugs (especially Doxazosin) as candidates for repurposing in AD treatment, warranting further investigation and clinical assessment.

Research progress of boron-containing drugs / 中国药科大学学报

@#In recent years, the research on boron-containing drugs, especially boric acid drugs, has been increasing gradually.Boron-containing drugs, which have been a new area of research for pharmaceutical chemists in the development of new drugs, play an increasingly important anti-inflammatory, antibacterial, and anti-tumor role.At present, five boron-containing drugs have been approved, many are under clinical trials, and more are under investigation around the world, which has greatly expanded the application of boron in the research of new drugs.This paper introduces the characteristics of boron, and reviews the indications of representative boron-containing drugs in various research stages, their binding mechanisms with targets, and their progress after entering clinical trials, aiming to provide reference for further research on boron-containing drugs.

Research progress on small molecule kinase inhibitors / 药学学报

Protein kinases are intimately involved in the pathogenesis of many diseases such as cancer, inflammation, and autoimmune and neurological diseases. Therefore, kinases have been widely studied as drug targets over the past three decades. As of April, 2020, the FDA had approved 59 small molecule kinase inhibitors (SMKIs) in the emerging field of targeted drug therapy. This paper focuses on the biochemistry and pharmacology of these 59 SMKIs and 121 SMKIs for which structures can be retrieved and that are now in phase Ⅱ and Ⅲ clinical trials. In addition, this paper also conducts a simple analysis of several popular targets and their inhibitors.

Research progress of gene therapy in clinical application / 生物工程学报

In the 1960s, scientists first raised the idea of curing genetic diseases using gene therapy. This new conceptual strategy aimed to achieve a much longer therapeutic effect by introducing exogenous genetic materials into the patients. After more than five decades of ups and downs, gene therapy has been brought into a new era by those milestone breakthroughs in the 21st century. Here we reviewed and summarized the history and breakthroughs of gene therapy, including some critical clinical trials, approved drugs, and emerging gene editing techniques. We believe that with their unique advantages over traditional therapies, more gene therapies will become practical approaches to genetic diseases and benefit the entire human race.

Currently Available Non-Balloon Devices

Obesity and metabolic syndrome are known to have an impact on the economy. Obesity and metabolic syndrome affect about 40% population in the America alone, and with about 400 million obese adults in the world, obesity is a global concern. Moreover, the prevalence of overweight children is increasing. Bariatric surgery remains the gold standard for the treatment of obesity; however, endoscopic approaches may have a significant role in the management of metabolic syndrome and obesity. Until recently, many endoscopic methods have been introduced; however, few methods are used in practice, whereas others are under experimental research. Endoscopists have an important role in the treatment of obesity because endoscopic therapies have demonstrated their safety and efficacy over the past few years. Endoscopic bariatric therapies can be categorized as follows: space occupying, malabsorption, and gastric volume reduction. In this review, we summarize the currently available non-balloon type endoscopic procedure.

Immune based therapy for melanoma.

A few years ago therapeutic options in advanced melanoma were very limited and the prognosis was somber. Although recent progresses are far from providing a cure for advanced melanoma, yet these have kindled new hopes and searching for a cure does not seem unreasonable. Seven new medicines have been authorized in various regions of the world in the recent past in the therapy of advanced melanoma, over half of them acting by mechanisms involving the immune system of the host. The anti-CTLA-4 (cytotoxic T lymphocyte associated protein-4) ipilimumab has been followed by anti-PD1 (programmed death1) inhibitors, more effective and safer. Very recently, the first oncolytic immunotherapy, talimogene laherparepvec (T-VEC) has been authorized for placing on the market and a variety of combinations of the new therapies are currently being evaluated or considered. Besides, a plethora of other molecules and approaches, especially monoclonal antibodies, are in the preliminary phases of clinical investigation and are likely to bring new benefits for the treatment of this potentially fatal form of cancer.

Websites of Three Approved Online Pharmacies:A Comparative Study / 中国药房

OBJECTIVE: To propose some suggestions towards the operation and development of online pharmacies in China.METHODS: From the following three aspects: website design,information provision,and customer service,the paper introduced and compared the websites of three approved online pharmacies,which include Jingwei Pharmacy,Shanghai Pharmacy and Jinxiang Pharmacy.RESULTS & CONCLUSIONS: To develop online pharmacies,the information display should be customer-centered,new marketing plans based on the characteristics of the internet should be developed;meanwhile,the operators of online pharmacies should help consumers developing an awareness of drug safety and offer them corresponding services.

Medical termination of pregnancy (amendment) act, 2002 an answer to mother's health & 'female foeticide'.

Human groups have, since early times, developed attitudes against the willful destruction of a foetus. At the same time, they have also recognized its permissibility in exceptional circumstances. Abortion raises a variety of medical, legal, ethical, and social issues. Indian Law recognizes the foetus as a special aggregation of cells with a potential for independent life and in this way protects the rights of 'unborn child'. This paper deals with issues related to abortion laws, reasons for their enactments, amendments and failure to implement, misuse by quacks, with special reference to The Medical Termination of Pregnancy (Amendment) Act, 2002, and Rules & Regulations, 2003. Thus, an attempt to answer for related questions either not discussed earlier or not answered effectively and clearly so that problem of increased rate of maternal mortality & morbidity' and 'female foeticide' could be dealt with effectively.

Harmonization of the Medical Specialist Certification System and the New Postgraduate Clinical Training System in Japan / 医学教育

Each medical specialist certification system in internal medicine and its subspecialities was founded and controled byeach medical society, but not by the public. Thus, each system had not been harmonized each other, and not recognizedas the public system until the the Ministry of Health, Labour and Welfare (MHLW)'s declaration of permission for publicnotification of each certificated medical speciality when approved according to their criterion. Based on the longstandingdiscussion and negotiation in the special committee on internal medicine of the Japanese Board of MedicalSpecialist, on the other hand, the Japanese Society of Internal Medicine (JSIM) and the societies of subspecialities in theinternal medical fields agreed to build up the so-called 2 stair-system as the framework of medical specialist certificationsystem, where the Certified Member of the JSIM is inevitable for application or renewal of the Fellow of the JSIM andother certifications of medical specialist of the internal medical subspecialities. In face to the new compulsory postgraduateclinical training system with super-rotation for 2 years starting from 2004 fisical year, JSIM decided that 2 yearpostgraduate clinical training is included to the 3 year training period necessary for the application of the Board CertifiedMember of JSIM, because clinical training with super-rotaion system aimed to master the capability of primary medicalcare is recognized to be also an essential part of the training program for internists. For the better medical specialist certificationsystem in the future, the Japanese Board of Medical Specialist should be approved to be the public and independentorganization for quality control of Japanese medical specialist certification system as a whole to improve medicaland welfare quality which fit for the requirement of Japanese people in the 21th century.

Analysis of Work-Related Musculoskeletal Disease by Approved Korea Labor Welfare Corporation in 1999 / 대한산업의학회지

OBJECTIVES: The purpose of this study was to analyze the characteristics of workrelated musculoskeletal diseases, as listed by the Korea Labor Welfare Corporation (KLWC). METHODS: Using the database of the KLWC, we collected information from 410 approved occupational musculoskeletal disease cases, which occurred between 1 January and 31 December 1999 and were approved by 30 June in 2000. We investigated the characteristics of the disease using a mail survey and telephone interviews. The characteristics we investigated included : sex, age, disease-related working duration, process of disease occurrence, type of enterprises, etc. RESULTS: Men accounted for 75.6 % (310 workers) of the approved cases. The most common age group was 30-39 years (n=143, 34.9 %). The mean disease-related working duration was 5.7 years, and the most commonly had a work-duration of 1-5 years (n=108, 36.0 %). The major industrial types of enterprise were manufacturing (235 workers, 57.3 %), transportation (46 workers, 11.2 %), and construction (25 workers, 6.1 %). Within the manufacturing industry, the most common was motor vehicles and trailers manufacturing. Within the group, the most common jobs were plant or machine operators and assemblers (129 workers, 36.5 %), elementary occupations (90 workers, 25.5 %), and craft and related trades workers (63 workers, 17.8 %). The majority of the diseases involved lumbar problems (232 cases, 54.7 %), neck and upper extremity diseases (183 cases, 43.2 %) and lower extremity diseases (9 cases, 2.1 %). In the cases of lumbar disease, the mean age and working duration was 36.5 years and 4.7 years, respectively. Fifty-four cases of lumbar diseases were due to repetitive work and 89 due to non-repetitive work. Bad posture at work was the most common cause for those doing repetitive work(23 cases), and lifting the most common cause of problems in the non-repetitive work cases (27). CONCLUSIONS: We were able to elucidate the characteristics of workers with approved occupational musculoskeletal disease through this study. Many approved cases occurred in women, and workers performing repetitive work, of these herniated nucleus pulposus occurred in many workers performing simple repetitive works without serious external forces. This suggests that a prevention policy for occupational musculoskeletal disease must be established, to focusing on the above-mentioned high-risk groups.

Analysis of Occupational Disease by Approved Korea Labor Welfare Corporation in 1999 / 대한산업의학회지

OBJECTIVES: The purpose of this study is to analyze the characteristics of occupational diseases listed by Korea Labor Welfare Corporation(KLWC). METHODS: Using the database of the KLWC, we collected 575 approved occupational disease cases occurring between 1 January and 31 December 1999 and approved by the thirtieth June in 2000. We investigated the characteristics(sex, age, occupational history, kinds of occupational disease, exposure material, type of enterprises, etc.) of occupational disease using a mail survey and telephone interviews. RESULTS: Men accounted for 88.9 %(511 workers) of the approved cases. 56 cases(9.7%) died of occupational disease. The most common age group was 50~59 years of age(n=217, 37.7 %). The proportion of workers with grater than ten years disease related working condition exposure were 195(49.0 %). The majority of diseases were respiratory problems(211 workers, 22.4 %), occupational hearing loss(149 workers, 25.9 %), infectious disease(69 workers, 12.0 %), intoxication(60 workers, 10.4 %), skin disease(29 workers, 5.0 %) and cancer(17 workers, 3.0 %). The causal hazardous agents were dusts(209 cases, 36.3 %), physical agents(157 cases, 27.3 %), chemical agents(89 cases, 16.3 %), biological agents(82 cases, 14.3 %) and workrelated agents(34 cases, 5.9 %). The major types of enterprise were manufacturing(262 workers, 45.6 %), mining and quarrying(174 workers, 30.3 %), public administration(42 workers, 7.3 %) and the health care industry(28 workers, 4.9 %). The kinds of job included craft and related trades workers(285 workers, 49.6 %), plant or machine operators and assemblers(139 workers, 24.2 %), elementary occupations(72 workers, 12.5 %) and professionals(28 workers, 4.9 %). CONCLUSIONS: We were able to elucidate the kinds of occupational disease and the characteristics of workers through this study. Many approved cases occurred among nonmanufacturing and non-mining workers and the kinds of disease were varied. This suggests that management policy must be established to prevent occupational disease occurring among workers in the above type of industries.