Invention Of New Drugs Research Articles

Molecular modelling of DNA cytosine methylation

Epigenetic modifications are significant processes controlling gene expression. Since their discovery by C. H. Waddington, several multisubject research proceeded and allowed investigation of how biochemical regulations can influence gene transcription. The main epigenetic modification is DNA methylation. This catalytic process of attaching methyl groups to nucleobases (mostly cytosine) is fundamental for the regulation of gene expression and chromatin accessibility. Methylated parts of the genome, which are mostly gene promoters and enhancers, are silenced due to specific biological mechanisms. Scientists postulate that aberrant DNA methylation and other epigenetic modifications can contribute to the development of diverse pathologies such as Alzheimer's disease, epilepsy, Schizophrenia, tumorigenesis, and atherosclerosis. Due to these discoveries, it is important to characterize in detail the mechanism of epigenetic modifications to develop new possible ways of treatment. In this work, we presented complex studies of DNA methylation mechanism including dynamic and energetic analysis of the reaction system. A cluster chemical approach was used to model the active site of enzyme catalyzing methylation - DNMT1 (DNA methyltransferase 1). The created model was subjected to quantum chemical calculations. Geometry optimization was performed with ADF software, providing an energetic characterization of the studied process. Dynamic properties of the enzyme model were described due to molecular dynamics (MD) procedures performed with CP2K software. MD calculations were focused on the observation and description of proton transfer between glutamate acid and cytosine, which is considered the main enzyme-substrate interaction leading to the creation of 5-methylcytosine 5mC (product of the studied reaction) and covalent bonding between enzymes cysteine and nucleobase. This research provides a comprehensive understanding of the DNA methylation mechanism and may contribute to the invention of new drugs and modern ways of treatment.

RNAi Technology and Investigation on Possible Vaccines to Combat SARS-CoV-2 Infection.

Coronavirus disease of 2019 (COVID-19) pandemic, taking place globally, occurs as a result of the SARS-CoV-2 viral infection which has caused death of innumerable numbers of people and is responsible for a massive drop in the global economy. Millions of people are infected, and the death rate is also quite high in different countries. So, there is an urgent requirement of the invention of some effective and efficient drugs that can be effective against this deadly viral infection. The invention of new drugs and vaccine has become a matter of utmost importance to stop the mayhem of coronavirus pandemic. In the middle of such a deadly pandemic, the necessity of development of a vaccine is of high importance in this context. Among all the popular methods of vaccine development, the mRNA vaccines turned out to be the one of the most versatile vaccine with quick responses. However, in this review, we have explained all the possible types of vaccines available including DNA vaccines, RNA vaccines, and live and attenuated vaccines. Their effectiveness, importance, and application of the vaccines against the SARS-CoV-2 virus have been discussed. Research is also being conducted in the field of gene silencing, and one of the best possible ways to combat the virus at the molecular level is by applying RNAi technology. The modified siRNA molecules can be used to silence the gene expression of the virus. A summarization of the virus’s behavior, characteristics, and the methods by which RNAi technology can be administered to control the virus is depicted in this study.

Conditions of Legality of Medical Human Subject Research

The article examines international acts and national legislation and highlights the conditions for the legality of medical research with human participation.
 The provisions of the Nuremberg Code (1947), the Helsinki Declaration of the World Medical Association «Ethical principles for medical research involv- ing human subjects» (1964), the Universal Declaration on the Human Genome and Human Rights (1997), the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (1997) and the Addi- tional Protocols to the Convention, Regulation of the European Parliament and of the Council (EU) No 536/2014. The support of the recommendation to ratify the Convention on Human Rights and Biomedicine and its additional protocols in Ukraine has been expressed.
 It has been established that international acts stipulate that the design and implementation of each human subject research must be clearly described in the research protocol. In addition, research protocols must be subject to prior review by the Ethics Committees.
 It has been substantiated that international acts set for medical research standards, which are based on the principles of respect for dignity and human rights, the priority of interests of the person over the interests of society or sci- ence, compliance with safety requirements and prevention of harm to humans, mandatory permission to conduct medical examination, research and control- lability of the research process and its results, compensation for any damage caused by medical research.
 Conditions of legality of medical research can be divided into general (obser- vance of which is always necessary if a person participates in experiments) and special (additional conditions of legality, which are put forward depend- ing on the field or object of research, namely in the field of experiments com- bined with medical care , human genome research, in vitro embryo research, in the field of clinical trials of drugs).

Continuing Professional Development for Doctors in Pakistan is need of the hour

In Pakistan, health professionals get their professional undergraduate and postgraduate qualifications after thorough training and assessment criteria as defined by their respective national regulatory bodies. These qualifications help them get registered and get a license for clinical practice in their respective domains. Any registrations and licenses are renewed by paying the prescribed fee without any requirements for reassessment or recertifications. Over the last few decades, health sciences have shown rapid advancements with the invention of new drugs and technologies. Due to this exponential increase in knowledge, no practitioner can hope to remain competent for more than a few years after graduation without a program of active learning. As such, a well-structured and regulated program of lifelong learning must be followed by all health professionals. To keep health professionals abreast with these changes and to ensure the maintenance of certain minimum competencies, there is a need for Continuing Professional Development (CPD) to be implemented at the national level with strict regulatory compliance. According to World Federation for Medical Education (World Federation for Medical Education, 2015), Continuing Professional Development (CPD) is a process of education and training commencing after completion of basic and postgraduate medical education, thereafter, continuing as long as the health professional is engaged in professional activities. CPD mainly implies self-directed and practice-based learning activities in addition to supervised education, and rarely involves supervised training for an extended period of time. The terms ‘Continuing Medical Education (CME)’ and ‘Continuing Professional Development (CPD)’ are often used synonymously.

Entangled Conditional Adversarial Autoencoder for de Novo Drug Discovery.

Modern computational approaches and machine learning techniques accelerate the invention of new drugs. Generative models can discover novel molecular structures within hours, while conventional drug discovery pipelines require months of work. In this article, we propose a new generative architecture, entangled conditional adversarial autoencoder, that generates molecular structures based on various properties, such as activity against a specific protein, solubility, or ease of synthesis. We apply the proposed model to generate a novel inhibitor of Janus kinase 3, implicated in rheumatoid arthritis, psoriasis, and vitiligo. The discovered molecule was tested in vitro and showed good activity and selectivity.

DECLINE IN INVITRO BIO-ASSAY METHODS IN PHARMACOLOGY: A WORRISOME TREND

Among the various definitions of pharmacology, either at molecular or cellular levels , it is clear that it involves studies which focuses on drugs and chemical agents interactions in man, organisms, cells, physiological processes , and environment, be it invivo or invitro ,The tasks for pharmacologists also involve investigations through experimental studies , into possible development or invention of new drugs. In Research therefore, the focus is rooted on targeting components rather systems(organisms, tissues,and cells are composed of molecular components), however as they interact with each other they form a system (BLACK, 2010..). The question therefore, is HOW CAN WE STUDY COMPLEX SYSTEM IN THE LABORATORY?. The traditional use of Isolated tissue or whole organ system preparations in most pharmacological studies in African universities especially in Nigeria has given way to a more recent molecular biology, thereby loosing focus on the techniques and skills in the classical organ-bath methods. This presentation highlights the problem confronting the use of these methods and call for support from advanced laboratories to help refocus studies in invitro and invitro techniques methods.

Современные подходы к лечению первичных malt-лимфом желудка

Main idea of this article is to make a short overview of modern MALT lymphoma treatment approaches. Historically, surgery was the leading treatment modality. Discovery of H.pylori involvement, invention of new drugs and chemotherapy protocols, wide use of monoclonal antibodies, significantly raised the effectiveness of conservative treatment. Routine use of CT scanning, invention of conformal, precise radiotherapy techniques allowed to achieve fine radiotherapy treatment results, especially in the case of combined chemo – radiotherapy protocols. That is why nowadays conservative treatment plays more significant role. However, complete remission cannot be achieved in all the cases. More research is required and thorough analyze of advantages and disadvantages of every technique and their combinations.

Patents and Pharmaceutical Drugs: Understanding the Pressures on Developing Countries

This paper offers a discussion to the question of why there are pressures on developing countries for introducing and/or reinforcing patent protection to pharmaceutical drugs. Patent protection is an important component of a complex strategy developed by the research and development intensive pharmaceutical drug companies of industrial countries to meet market competition. For legal and economic reasons, patents are fundamental instruments for allowing the drug-inventing companies to appropriate the returns from their inventions. Patents sustain high prices, which in turn provide rents to undertake further research and development, which in turn allows the invention of new drugs, etc. In recent years, increasing drug regulations have implied that effective patent protection to the research and development intensive pharmaceutical drug companies has eroded. Furthermore, competition from the generic drug companies has increased quite significantly. Restoring patent protection in industrial countries and making developing countries introduce patent protection, has become part of research and development intensive pharmaceutical companies' strategies to regain market share.