Epidemiological Trends and Current Challenges in Ebola: Pathogen Biology, Drug Targets, and Therapeutic Strategies

2019 ◽  
pp. 251-282
Author(s):  
Sandeep Sharma ◽  
Jeena Gupta
Keyword(s):  
Drug Targets ◽  
Therapeutic Strategies ◽  
Epidemiological Trends

scholarly journals Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyondβ-Amyloid: Insights from Clinical Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-22 ◽  
Author(s):  
Qiutian Jia ◽  
Yulin Deng ◽  
Hong Qing
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Drug Targets ◽  
Neurodegenerative Disorder ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Drug Candidates ◽  
Effective Drugs ◽  
Novel Drug

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with two hallmarks:β-amyloid plagues and neurofibrillary tangles. It is one of the most alarming illnesses to elderly people. No effective drugs and therapies have been developed, while mechanism-based explorations of therapeutic approaches have been intensively investigated. Outcomes of clinical trials suggested several pitfalls in the choice of biomarkers, development of drug candidates, and interaction of drug-targeted molecules; however, they also aroused concerns on the potential deficiency in our understanding of pathogenesis of AD, and ultimately stimulated the advent of novel drug targets tests. The anticipated increase of AD patients in next few decades makes development of better therapy an urgent issue. Here we attempt to summarize and compare putative therapeutic strategies that have completed clinical trials or are currently being tested from various perspectives to provide insights for treatments of Alzheimer’s disease.

scholarly journals Pulmonary Edema in COVID-19 Patients: Mechanisms and Treatment Potential

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyu Cui ◽  
Wuyue Chen ◽  
Haoyan Zhou ◽  
Yuan Gong ◽  
Bowen Zhu ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Pulmonary Edema ◽  
Drug Targets ◽  
Direct Consequence ◽  
Healthcare Services ◽  
Therapeutic Strategies ◽  
Fluid Accumulation ◽  
Proper Management ◽  
Assisted Respiration

COVID-19 mortality is primarily driven by abnormal alveolar fluid metabolism of the lung, leading to fluid accumulation in the alveolar airspace. This condition is generally referred to as pulmonary edema and is a direct consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are multiple potential mechanisms leading to pulmonary edema in severe Coronavirus Disease (COVID-19) patients and understanding of those mechanisms may enable proper management of this condition. Here, we provide a perspective on abnormal lung humoral metabolism of pulmonary edema in COVID-19 patients, review the mechanisms by which pulmonary edema may be induced in COVID-19 patients, and propose putative drug targets that may be of use in treating COVID-19. Among the currently pursued therapeutic strategies against COVID-19, little attention has been paid to abnormal lung humoral metabolism. Perplexingly, successful balance of lung humoral metabolism may lead to the reduction of the number of COVID-19 death limiting the possibility of healthcare services with insufficient capacity to provide ventilator-assisted respiration.

scholarly journals Epithelial-Mesenchymal Transition (EMT) as a Therapeutic Target

2021 ◽  
pp. 1-26
Author(s):  
Sven Jonckheere ◽  
Jamie Adams ◽  
Dominic De Groote ◽  
Kyra Campbell ◽  
Geert Berx ◽  
...  
Keyword(s):  
Cancer Cells ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Epithelial Mesenchymal Transition ◽  
Primary Tumour ◽  
Therapy Resistance ◽  
Therapeutic Strategies ◽  
The Body ◽  
Screening Tools ◽  
Mesenchymal Transition

Metastasis is the spread of cancer cells from the primary tumour to distant sites and organs throughout the body. It is the primary cause of cancer morbidity and mortality, and is estimated to account for 90% of cancer-related deaths. During the initial steps of the metastatic cascade, epithelial cancer cells undergo an epithelial-mesenchymal transition (EMT), and as a result become migratory and invasive mesenchymal-like cells while acquiring cancer stem cell properties and therapy resistance. As EMT is involved in such a broad range of processes associated with malignant transformation, it has become an increasingly interesting target for the development of novel therapeutic strategies. Anti-EMT therapeutic strategies could potentially not only prevent the invasion and dissemination of cancer cells, and as such prevent the formation of metastatic lesions, but also attenuate cancer stemness and increase the effectiveness of more classical chemotherapeutics. In this review, we give an overview about the pros and cons of therapies targeting EMT and discuss some already existing candidate drug targets and high-throughput screening tools to identify novel anti-EMT compounds.

Recent Advances in Combretastatin A-4 Inspired Inhibitors of Tubulin Polymerization-An Update

2022 ◽  
Vol 29 ◽  
Author(s):  
Sultan Nacak Baytas
Keyword(s):  
Drug Targets ◽  
Therapeutic Strategies ◽  
Tubulin Polymerization ◽  
Molecular Chemistry ◽  
Microtubule Polymerization ◽  
Colchicine Binding Site ◽  
Microtubule Targeting Agents ◽  
Genomics And Proteomics ◽  
Potential Drug Targets ◽  
Structural Simplicity

Abstract: Cancer is one of the leading causes of fatality and mortality worldwide. Investigations on developing therapeutic strategies for cancer are supported throughout the world. The massive achievements in molecular sciences involving biochemistry, molecular chemistry, medicine, and pharmacy, and high throughput techniques such as genomics and proteomics have helped to create new potential drug targets for cancer treatment. Microtubules are very attractive targets for cancer therapy because of the crucial roles they play in cell division. In recent years, lots of efforts have been put into the identification of new microtubule-targeting agents (MTAs) in anticancer therapy. Combretastatin A-4 (CA-4) is a natural compound that binds to microtubules’ colchicine binding site and inhibits microtubule polymerization. Due to CA-4’s structural simplicity, many analogs have been synthesized. This article summarizes the new molecule development efforts to reach CA-4 analogs by modifications on its pharmacophore groups, published since 2015.

scholarly journals The role of caspase-8 in the tumor microenvironment of ovarian cancer

2020 ◽  
Author(s):  
Izabela Kostova ◽  
Ranadip Mandal ◽  
Sven Becker ◽  
Klaus Strebhardt
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Tumor Microenvironment ◽  
Drug Targets ◽  
Immune Cell ◽  
Lymphocyte Activation ◽  
Therapeutic Strategies ◽  
Signal Pathways ◽  
Caspase 8 ◽  
Immune Resistance

Abstract Caspase-8 is an aspartate-specific cysteine protease, which is best known for its apoptotic functions. Caspase-8 is placed at central nodes of multiple signal pathways, regulating not only the cell cycle but also the invasive and metastatic cell behavior, the immune cell homeostasis and cytokine production, which are the two major components of the tumor microenvironment (TME). Ovarian cancer often has dysregulated caspase-8 expression, leading to imbalance between its apoptotic and non-apoptotic functions within the tumor and the surrounding milieu. The downregulation of caspase-8 in ovarian cancer seems to be linked to high aggressiveness with chronic inflammation, immunoediting, and immune resistance. Caspase-8 plays therefore an essential role not only in the primary tumor cells but also in the TME by regulating the immune response, B and T lymphocyte activation, and macrophage differentiation and polarization. The switch between M1 and M2 macrophages is possibly associated with changes in the caspase-8 expression. In this review, we are discussing the non-apoptotic functions of caspase-8, highlighting this protein as a modulator of the immune response and the cytokine composition in the TME. Considering the low survival rate among ovarian cancer patients, it is urgently necessary to develop new therapeutic strategies to optimize the response to the standard treatment. The TME is highly heterogenous and provides a variety of opportunities for new drug targets. Given the variety of roles of caspase-8 in the TME, we should focus on this protein in the development of new therapeutic strategies against the TME of ovarian cancer.

scholarly journals Development of a Multi-Target Strategy for the Treatment of Vitiligo via Machine Learning and Network Analysis Methods

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiye Wang ◽  
Lin Luo ◽  
Qiong Ding ◽  
Zengrui Wu ◽  
Yayuan Peng ◽  
...  
Keyword(s):  
Network Analysis ◽  
Drug Targets ◽  
Characteristic Curve ◽  
Therapeutic Targets ◽  
Mapk Signaling ◽  
Therapeutic Strategies ◽  
Antioxidant Systems ◽  
Proteomic Profiling ◽  
Drug Candidates ◽  
Target Strategy

Vitiligo is a complex disorder characterized by the loss of pigment in the skin. The current therapeutic strategies are limited. The identification of novel drug targets and candidates is highly challenging for vitiligo. Here we proposed a systematic framework to discover potential therapeutic targets, and further explore the underlying mechanism of kaempferide, one of major ingredients from Vernonia anthelmintica (L.) willd, for vitiligo. By collecting transcriptome and protein-protein interactome data, the combination of random forest (RF) and greedy articulation points removal (GAPR) methods was used to discover potential therapeutic targets for vitiligo. The results showed that the RF model performed well with AUC (area under the receiver operating characteristic curve) = 0.926, and led to prioritization of 722 important transcriptomic features. Then, network analysis revealed that 44 articulation proteins in vitiligo network were considered as potential therapeutic targets by the GAPR method. Finally, through integrating the above results and proteomic profiling of kaempferide, the multi-target strategy for vitiligo was dissected, including 1) the suppression of the p38 MAPK signaling pathway by inhibiting CDK1 and PBK, and 2) the modulation of cellular redox homeostasis, especially the TXN and GSH antioxidant systems, for the purpose of melanogenesis. Meanwhile, this strategy may offer a novel perspective to discover drug candidates for vitiligo. Thus, the framework would be a useful tool to discover potential therapeutic strategies and drug candidates for complex diseases.

scholarly journals A Conserved Machinery Underlies the Synthesis of a Chitosan Layer in the Candida Chlamydospore Cell Wall

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Leo D. Bemena ◽  
Kyunghun Min ◽  
James B. Konopka ◽  
Aaron M. Neiman
Keyword(s):  
Cell Wall ◽  
Cell Walls ◽  
Drug Targets ◽  
Therapeutic Strategies ◽  
Effective Strategy ◽  
Fungal Cell ◽  
Detailed Understanding ◽  
Cell Wall Assembly ◽  
Wall Assembly ◽  
Potential Drug Targets

The cell wall is the interface between the fungal cell and its environment and disruption of cell wall assembly is an effective strategy for antifungal therapies. Therefore, a detailed understanding of how cell walls form is critical to identify potential drug targets and develop therapeutic strategies.

scholarly journals Indoleamine 2,3-Dioxygenase 1: A Promising Therapeutic Target in Malignant Tumor

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaotian Song ◽  
Qianqian Si ◽  
Rui Qi ◽  
Weidan Liu ◽  
Miao Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Targets ◽  
Biological Function ◽  
Malignant Tumors ◽  
Therapeutic Strategies ◽  
Comprehensive Analysis ◽  
The Other ◽  
Indoleamine 2,3 Dioxygenase ◽  
Promising Therapeutic Target ◽  
Multistep Process

Tumorigenesis is a complex multifactorial and multistep process in which tumors can utilize a diverse repertoire of immunosuppressive mechanisms to evade host immune attacks. The degradation of tryptophan into immunosuppressive kynurenine is considered an important immunosuppressive mechanism in the tumor microenvironment. There are three enzymes, namely, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1), and indoleamine 2,3-dioxygenase 2 (IDO2), involved in the metabolism of tryptophan. IDO1 has a wider distribution and higher activity in catalyzing tryptophan than the other two; therefore, it has been studied most extensively. IDO1 is a cytosolic monomeric, heme-containing enzyme, which is now considered an authentic immune regulator and represents one of the promising drug targets for tumor immunotherapy. Collectively, this review highlights the regulation of IDO1 gene expression and the ambivalent mechanisms of IDO1 on the antitumoral immune response. Further, new therapeutic targets via the regulation of IDO1 are discussed. A comprehensive analysis of the expression and biological function of IDO1 can help us to understand the therapeutic strategies of the inhibitors targeting IDO1 in malignant tumors.

Identification of Novel Key Targets and Candidate Drugs in Oral Squamous Cell Carcinoma

2020 ◽  
Vol 15 (4) ◽  
pp. 328-337
Author(s):  
Juan Liu ◽  
Xinjie Lian ◽  
Feng Liu ◽  
Xueling Yan ◽  
Chunyan Cheng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Network Analysis ◽  
Virtual Screening ◽  
Oral Squamous Cell Carcinoma ◽  
Small Molecules ◽  
Cell Carcinoma ◽  
Candidate Genes ◽  
Squamous Cell ◽  
Drug Targets ◽  
Therapeutic Strategies

Background: Oral Squamous Cell Carcinoma (OSCC) is the most common malignant epithelial neoplasm. It is located within the top 10 ranking incidence of cancers with a poor prognosis and low survival rates. New breakthroughs of therapeutic strategies are therefore needed to improve the survival rate of OSCC harboring patients. Objective: Since targeted therapy is considered as the most promising therapeutic strategies in cancer, it is of great significance to identify novel targets and drugs for the treatment of OSCC. Methods: A series of bioinformatics approaches were launched to identify the hub proteins and their potential agents. Microarray analysis and several online functional activity network analysis were firstly utilized to recognize drug targets in OSCC. Subsequently, molecular docking was used to screen their potential drugs from the specs chemistry database. At the same time, the assessment of ligand-based virtual screening model was also evaluated. Results: In this study, two microarray data (GSE31056, GSE23558) were firstly selected and analyzed to get consensus candidate genes including 681 candidate genes. Additionally, we selected 33 candidate genes based on whether they belong to the kinases and transcription factors and further clustered candidate hub targets based on functions and signaling pathways with significant enrichment analysis by using DAVID and STRING online databases. Then, core PPI network was then identified and we manually selected GRB2 and IGF1 as the key drug targets according to the network analysis and previous references. Lastly, virtual screening was performed to identify potential small molecules which could target these two targets, and such small molecules can serve as the promising candidate agents for future drug development. Conclusion: In summary, our study might provide novel insights for understanding of the underlying molecular events of OSCC, and our discovered candidate targets and candidate agents could be used as the promising therapeutic strategies for the treatment of OSCC.

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