scholarly journals Hypothesis for changing models: current pharmaceutical paradigms, trends and approaches in drug discovery

2015 ◽  
Author(s):  
Domenico Fuoco
Keyword(s):  
Scientific Reasoning ◽  
Molecular Mechanisms ◽  
Annual Number ◽  
Web Based ◽  
Chemical Structures ◽  
New Drug ◽  
New Chemical Entities ◽  
The Usa ◽  
Total Investment

Despite the increasing availability of chemicals, the number of New Drug Approvals (NDA) from the Food and Drug Administration (FDA) remains unchanged. The number of chemical structures available online via web-based open source applications will reach the symbolic 1 billion in the 10 next years. However, for no apparent reasons, the number of NDA accepted yearly has not changed in the past 25 years. One of the emerging paradigms of Big Pharma is that the more we know about molecular mechanisms and cell signaling pathways, the less we understand how to use this knowledge to make New Chemical Entities (NCE). Moreover, the annual number of pharmaceutical patents collected in the OCSE database has virtually not increased. Unexpectedly, the number of patents originating in the USA is decreasing significantly, while Asia is doing very well. The comparison between the number of NCEs and the American investment in Research and Development (R&D) in the last 35 years shows that to obtain a new drug blockbuster, the total investment is quasi 4 USD billion. One of the peculiarities is the inverse relationship between the investment in R&D and the continued shortfall in productivity. A main reason for this decline is that the quality of scientific reasoning done by experienced chemists is too often replaced by Big Data . It is time to change the role of chemistry in Big Pharma and to re-position it as the central science to progress and to lead to much needed innovation.

scholarly journals Hypothesis for changing models: current pharmaceutical paradigms, trends and approaches in drug discovery

2015 ◽  
Author(s):  
Domenico Fuoco
Keyword(s):  
Scientific Reasoning ◽  
Molecular Mechanisms ◽  
Annual Number ◽  
Web Based ◽  
Chemical Structures ◽  
New Drug ◽  
New Chemical Entities ◽  
The Usa ◽  
Total Investment

Despite the increasing availability of chemicals, the number of New Drug Approvals (NDA) from the Food and Drug Administration (FDA) remains unchanged. The number of chemical structures available online via web-based open source applications will reach the symbolic 1 billion in the 10 next years. However, for no apparent reasons, the number of NDA accepted yearly has not changed in the past 25 years. One of the emerging paradigms of Big Pharma is that the more we know about molecular mechanisms and cell signaling pathways, the less we understand how to use this knowledge to make New Chemical Entities (NCE). Moreover, the annual number of pharmaceutical patents collected in the OCSE database has virtually not increased. Unexpectedly, the number of patents originating in the USA is decreasing significantly, while Asia is doing very well. The comparison between the number of NCEs and the American investment in Research and Development (R&D) in the last 35 years shows that to obtain a new drug blockbuster, the total investment is quasi 4 USD billion. One of the peculiarities is the inverse relationship between the investment in R&D and the continued shortfall in productivity. A main reason for this decline is that the quality of scientific reasoning done by experienced chemists is too often replaced by Big Data . It is time to change the role of chemistry in Big Pharma and to re-position it as the central science to progress and to lead to much needed innovation.

scholarly journals Global Trends in Research of Macrophages Associated With Acute Lung Injury Over Past 10 Years: A Bibliometric Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Sheng Wang ◽  
Huanping Zhou ◽  
Li Zheng ◽  
Wanli Zhu ◽  
Lina Zhu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bibliometric Analysis ◽  
Scientific Output ◽  
Annual Number ◽  
Global Trends ◽  
Citation Score ◽  
The Past ◽  
The Usa

Acute lung injury (ALI) is an intractable disorder associated with macrophages. This bibliometric analysis was applied to identify the characteristics of global scientific output, the hotspots, and frontiers about macrophages in ALI over the past 10 years. We retrieved publications published from 2011 to 2020 and their recorded information from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC). Bibliometrix package was used to analyze bibliometric indicators, and the VOSviewer was used to visualize the trend and hotspots of researches on macrophages in ALI. Altogether, 2,632 original articles were reviewed, and the results showed that the annual number of publications (Np) concerning the role of macrophages in ALI kept increasing over the past 10 years. China produced the most papers, the number of citations (Nc) and H-index of the USA ranked first. Shanghai Jiaotong University and INT IMMUNOPHARMACOL were the most prolific affiliation and journal, respectively. Papers published by Matute-Bello G in 2011 had the highest local citation score (LCS). Recently, the keywords “NLRP3” and “extracellular vesicles” appeared most frequently. Besides, researches on COVID-19–induced ALI related to macrophages seemed to be the hotspot recently. This bibliometric study revealed that publications related to macrophages in ALI tend to increase continuously. China was a big producer and the USA was an influential country in this field. Most studies were mainly centered on basic researches in the past decade, and pathways associated with the regulatory role of macrophages in inhibiting and attenuating ALI have become the focus of attention in more recent studies. What is more, our bibliometric analysis showed that macrophages play an important role in COVID-19–induced ALI and may be a target for the treatment of COVID-19.

scholarly journals Potential Role of the Inflammasome-Derived Inflammatory Cytokines in Pulmonary Fibrosis

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Rupa Biswas ◽  
Melisa Bunderson-Schelvan ◽  
Andrij Holian
Keyword(s):  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Adaptor Protein ◽  
Adaptive Immune ◽  
Fibrotic Process ◽  
Future Drug ◽  
The Usa ◽  
Adaptive Immune Systems

Pulmonary fibrosis is a progressive, disabling disease with mortality rates that appear to be increasing in the western population, including the USA. There are over 140 known causes of pulmonary fibrosis as well as many unknown causes. Treatment options for this disease are limited due to poor understanding of the molecular mechanisms of the disease progression. However, recent progress in inflammasome research has greatly contributed to our understanding of its role in inflammation and fibrosis development. The inflammasome is a multiprotein complex that is an important component of both the innate and adaptive immune systems. Activation of proinflammatory cytokines following inflammasome assembly, such as IL-1βand IL-18, has been associated with development of PF. In addition, components of the inflammasome complex itself, such as the adaptor protein ASC have been associated with PF development. Recent evidence suggesting that the fibrotic process can be reversed via blockade of pathways associated with inflammasome activity may provide hope for future drug strategies. In this paper we will give an introduction to pulmonary fibrosis and its known causes. In addition, we will discuss the importance of the inflammasome in the development of pulmonary fibrosis as well as discuss potential future treatment options.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

The Role of Web Based Accounting Online System 2.0 as the Company's Income and Expense Management

2017 ◽  
Vol 1 (1) ◽  
pp. 44-49
Author(s):  
Nur Azizah ◽  
Dedeh Supriyanti ◽  
Siti Fairuz Aminah Mustapha ◽  
Holly Yang
Keyword(s):  
Financial Management ◽  
Accounting System ◽  
Bank Account ◽  
Web Based ◽  
Online System ◽  
Version 2.0 ◽  
User Friendly ◽  
The Impact ◽  
A Company

In a company, the process of income and expense of money must have a profit-generating goal base. The success of financial management within the company, can be monitored from the ability of the financial management in managing the finances and utilize all the opportunities that exist with as much as possible with the aim to control the company's cash (cash flow) and the impact of generating profits in accordance with expectations. With a web-based online accounting system version 2.0, companies can be given the ease to manage money in and out of the company's cash. It has a user friendly system with navigation that makes it easy for the financial management to use it. Starting from the creation of a company's cash account used as a cash account and corporate bank account on the system, deletion or filing of cash accounts, up to the transfer invoice creation feature, receive and send money. Thus, this system is very effective and efficient in the management of income and corporate cash disbursements.   Keywords:​Accounting Online System, Financial Management, Cash and Bank

TAMM HORSFALL PROTEIN: THE MEN BEHIND THE EPONYM

2019 ◽  
Vol 23 (2) ◽  
pp. 117-119 ◽  
Author(s):  
D. N. Paskalev ◽  
B. T. Galunska ◽  
D. Petkova-Valkova
Keyword(s):  
Viral Replication ◽  
Research Team ◽  
Molecular Mechanisms ◽  
Thick Ascending Limb ◽  
Rockefeller Institute ◽  
The Usa ◽  
Natural Inhibitor ◽  
Simplex Virus ◽  
First Time ◽  
New Protein

Tamm–Horsfall Protein (uromodulin) is named after Igor Tamm and Franc Horsfall Jr who described it for the first time in 1952. It is a glycoprotein, secreted by the cells in the thick ascending limb of the loop of Henle. This protein will perform a number of important pathophysiological functions, including protection against uroinfections, especially caused by E. Сoli, and protection against formation of calcium concernments in the kidney. Igor Tamm (1922-1995) is an outstanding cytologist, virologist and biochemist. He is one of the pioneers in the study of viral replication. He was born in Estonia and died in the USA. In 1964 he was elected for a professorship in Rockefeller Institute for Medical Research, where has been working continuously. Since 1959, he became a head of the virology lab established by his mentor and co-author Franc Horsfall. In the course of studies on the natural inhibitor of viral replication, Tamm and Horsfall isolated and characterized biochemically a new protein named after their names. Franc Lappin Horsfall Jr (1906-1971) was a well-known clinician and virologist with remarkable achievements in internal medicine. He was born and died in the USA. He worked in the Rockefeller Hospital from 1934 to 1960, then in the Center for Cancer Research at the Sloan-Kettering Institute. Here he was a leader of a research team studying the molecular mechanisms of immunity, the effects of chemotherapy with benzimidazole compounds (together with I. Tamm), coxsackie viruses, herpes simplex virus, etc. 

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