scholarly journals [FOREWORD] Novel insight into various therapeutic strategy by the development of DDS

2015 ◽  
Vol 30 (1) ◽  
pp. 7-7
Author(s):  
Fumio Ito
Keyword(s):  
Therapeutic Strategy ◽  
Insight Into

scholarly journals Inhibiting the integrated stress response pathway prevents aberrant chondrocyte differentiation thereby alleviating chondrodysplasia

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Cheng Wang ◽  
Zhijia Tan ◽  
Ben Niu ◽  
Kwok Yeung Tsang ◽  
Andrew Tai ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Cell Fate ◽  
Therapeutic Strategy ◽  
Chondrocyte Differentiation ◽  
Integrated Stress Response ◽  
Stress Response Pathway ◽  
Skeletal Disorders ◽  
The Impact ◽  
Insight Into

The integrated stress response (ISR) is activated by diverse forms of cellular stress, including endoplasmic reticulum (ER) stress, and is associated with diseases. However, the molecular mechanism(s) whereby the ISR impacts on differentiation is incompletely understood. Here, we exploited a mouse model of Metaphyseal Chondrodysplasia type Schmid (MCDS) to provide insight into the impact of the ISR on cell fate. We show the protein kinase RNA-like ER kinase (PERK) pathway that mediates preferential synthesis of ATF4 and CHOP, dominates in causing dysplasia by reverting chondrocyte differentiation via ATF4-directed transactivation of Sox9. Chondrocyte survival is enabled, cell autonomously, by CHOP and dual CHOP-ATF4 transactivation of Fgf21. Treatment of mutant mice with a chemical inhibitor of PERK signaling prevents the differentiation defects and ameliorates chondrodysplasia. By preventing aberrant differentiation, titrated inhibition of the ISR emerges as a rationale therapeutic strategy for stress-induced skeletal disorders.

scholarly journals Skin and Gut Microbiome in Psoriasis: Gaining Insight Into the Pathophysiology of It and Finding Novel Therapeutic Strategies

2020 ◽  
Vol 11 ◽  
Author(s):  
Lihui Chen ◽  
Jie Li ◽  
Wu Zhu ◽  
Yehong Kuang ◽  
Tao Liu ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Therapeutic Strategies ◽  
Intestinal Microbiome ◽  
Core Microbiome ◽  
The Core ◽  
The World ◽  
Novel Therapeutic Strategies ◽  
Insight Into ◽  
Gaining Insight

Psoriasis affects the health of myriad populations around the world. The pathogenesis is multifactorial, and the exact driving factor remains unclear. This condition arises from the interaction between hyperproliferative keratinocytes and infiltrating immune cells, with poor prognosis and high recurrence. Better clinical treatments remain to be explored. There is much evidence that alterations in the skin and intestinal microbiome play an important role in the pathogenesis of psoriasis, and restoration of the microbiome is a promising preventive and therapeutic strategy for psoriasis. Herein, we have reviewed recent studies on the psoriasis-related microbiome in an attempt to confidently identify the “core” microbiome of psoriasis patients, understand the role of microbiome in the pathogenesis of psoriasis, and explore new therapeutic strategies for psoriasis through microbial intervention.

scholarly journals N-Heterocycles Scaffolds as Quorum Sensing Inhibitors. Design, Synthesis, Biological and Docking Studies

2020 ◽  
Vol 21 (24) ◽  
pp. 9512
Author(s):  
Alfredo Fuentes-Gutiérrez ◽  
Everardo Curiel-Quesada ◽  
José Correa-Basurto ◽  
Alberto Martínez-Muñoz ◽  
Alicia Reyes-Arellano
Keyword(s):  
Quorum Sensing ◽  
Therapeutic Strategy ◽  
Proper Time ◽  
Docking Studies ◽  
Chromobacterium Violaceum ◽  
Quorum Sensing Inhibition ◽  
Design Synthesis ◽  
Docking Simulations ◽  
Quorum Sensing Inhibitors ◽  
Insight Into

Quorum sensing is a communication system among bacteria to sense the proper time to express their virulence factors. Quorum sensing inhibition is a therapeutic strategy to block bacterial mechanisms of virulence. The aim of this study was to synthesize and evaluate new bioisosteres of N-acyl homoserine lactones as Quorum sensing inhibitors in Chromobacterium violaceum CV026 by quantifying the specific production of violacein. Five series of compounds with different heterocyclic scaffolds were synthesized in good yields: thiazoles, 16a–c, thiazolines 17a–c, benzimidazoles 18a–c, pyridines 19a–c and imidazolines 32a–c. All 15 compounds showed activity as Quorum sensing inhibitors except 16a. Compounds 16b, 17a–c, 18a, 18c, 19c and 32b exhibited activity at concentrations of 10 µM and 100 µM, highlighting the activity of benzimidazole 18a (IC50 = 36.67 µM) and 32b (IC50 = 85.03 µM). Pyridine 19c displayed the best quorum sensing inhibition activity (IC50 = 9.66 µM). Molecular docking simulations were conducted for all test compounds on the Chromobacterium violaceum CviR protein to gain insight into the process of quorum sensing inhibition. The in-silico data reveal that all 15 the compounds have higher affinity for the protein than the native AHL ligand (1). A strong correlation was found between the theoretical and experimental results.

1123 UNDERSTANDING INTEGRIN SIGNALLING DURING LIVER FIBROSIS PROVIDES INSIGHT INTO THEIR MODULATION AS A THERAPEUTIC STRATEGY TO TREAT THE DISEASE

2013 ◽  
Vol 58 ◽  
pp. S458
Author(s):  
K. Martin ◽  
J. Pritchett ◽  
E. Harvey ◽  
V. Athwal ◽  
C. Streuli ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Therapeutic Strategy ◽  
Insight Into

scholarly journals Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1-40) Fibrils

2018 ◽  
Author(s):  
Francesco Tavanti ◽  
Alfonso Pedone ◽  
Maria Cristina Menziani
Keyword(s):  
Therapeutic Strategy ◽  
Therapeutic Potential ◽  
Structure Stability ◽  
Insoluble Form ◽  
The Brain ◽  
Identification And Characterization ◽  
Insight Into

One of the principal hallmarks of Alzheimer’s disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists either in blocking the amyloid aggregation and/or destroying the already formed aggregates. Natural products have shown significant therapeutic potential as amyloid inhibitors from in vitro studies as well as in vivo animal tests. In this study, the interaction of five natural biophenols (curcumin, dopamine, (-)-Epigallocatechin-3-gallate, Quercetin, and Rosmarinic acid) with the amyloid-β(1-40) fibrils has been studied through computational simulations. The results allowed the identification and characterization of the different binding modalities of each compounds and their consequences on fibril dynamics and aggregation. It emerges that the lateral aggregation of the fibrils is strongly influenced by the intercalation of the ligands, which modulate the double-layered structure stability.

scholarly journals Patent Insight into the Development of Therapeutic Strategies against Coronaviruses

2021 ◽  
Vol 1 (1) ◽  
pp. 93-100
Author(s):  
Hai-Long Zhang ◽  
Ai-Feng Zhou ◽  
Yiqian Li
Keyword(s):  
Therapeutic Strategy ◽  
Vaccine Development ◽  
Rna Viruses ◽  
Therapeutic Strategies ◽  
Peptide Drugs ◽  
Leading Role ◽  
Global Pandemic ◽  
Effective Therapeutic Strategy ◽  
Insight Into ◽  
Development And Evolution

Coronaviruses are a group of RNA viruses, which cause diseases in humans. The emergence of COVID-19, has caused a global pandemic. It is focused on developing an effective therapeutic strategy against COVID-19. To better understand the development and evolution of therapeutic strategies against coronaviruses, we conducted US granted patents analysis. The results showed vaccines played a leading role in therapies against coronaviruses. Both attenuated vaccines and recombinant genetic vaccines were very important approaches in vaccine development against coronaviruses. It is not a rapid approach to develop peptide drugs against COVID-19 or future novel coronaviruses. The study was the first one to show the development and evolution in therapeutic strategies against coronaviruses based on patent insight. The present study provides a new insight into the development of therapeutic strategies against coronaviruses.

scholarly journals Pathways involved in pony body size development

2020 ◽  
Author(s):  
jun fang ◽  
yanru zhang ◽  
dong zhang ◽  
junwei cao ◽  
li zhang ◽  
...  
Keyword(s):  
Wnt Pathway ◽  
Therapeutic Strategy ◽  
Genetic Regulation ◽  
Body Growth ◽  
Long Bone ◽  
Hormone Regulation ◽  
Hormone Concentration ◽  
Mongolian Horse ◽  
Insight Into

Abstract Background: The mechanism of body growth in mammal s is poorly understood. Here, we report the regulat ory networks involv ed in body growth through analyzing transcriptomes of pituitary and epiphyseal tissues of Debao pon ies and Mongolian horse s at juvenile and adult stages . Results: We found that Growth hornome receptor ( GHR ) was expressed little in long bones though Growth hornome ( GH ) w as highly expressed in Debao pon ies compared with Mongolian horses. Moreover, m -RAS and ATF3 , involved in the GHR pathway , were found to be significant ly downreg ulated in juvenile pon ies , which slowed the proliferation of bone osteocytes. However, WNT2 and PLCβ2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of bone extracellular matrix. Furthermore, we found that the WNT/Ca 2+ pathway may be responsible for the regulation of body growth . W e then demonstrated that GHR was lack ing in long bone s of Debao ponies using RT-qPCR and Western blot. Treatment with WNT antagonist 1 decrease d expression of the WNT pathway (P ≤ 0.05) in vitro. The transduction of ATDC5 cells with GHR-RNAi lentivirus decrease d expression of the GHR pathway (P ≤ 0.05). Additionally, detection of plasma hormone concentration s showed that the pon ies had higher levels of IGF-1 as juvenile s and GH in adulthood than Mongolian horse s , indicating that the hormone regulation in Debao pon ies differ s from that in Mongolian horse s . Conclusion: Our work provides an insight into the genetic regulation for dwarf growth in mammals and a reference for therapeutic strategy for dwarfism.

scholarly journals IFN-III is selectively produced by cDC1 and predicts good clinical outcome in breast cancer

2020 ◽  
Vol 5 (46) ◽  
pp. eaav3942 ◽  
Author(s):  
Margaux Hubert ◽  
Elisa Gobbini ◽  
Coline Couillault ◽  
Thien-Phong Vu Manh ◽  
Anne-Claire Doffin ◽  
...  
Keyword(s):  
Immune Responses ◽  
Patient Outcomes ◽  
Therapeutic Strategy ◽  
Multidisciplinary Approach ◽  
Cytotoxic Lymphocyte ◽  
Primary Tumors ◽  
Ifn Γ ◽  
Type Iii Interferon ◽  
Precise Role ◽  
Insight Into

Dendritic cells play a key role in the orchestration of antitumor immune responses. The cDC1 (conventional dendritic cell 1) subset has been shown to be essential for antitumor responses and response to immunotherapy, but its precise role in humans is largely unexplored. Using a multidisciplinary approach, we demonstrate that human cDC1 play an important role in the antitumor immune response through their capacity to produce type III interferon (IFN-λ). By analyzing a large cohort of breast primary tumors and public transcriptomic datasets, we observed specific production of IFN-λ1 by cDC1. In addition, both IFN-λ1 and its receptor were associated with favorable patient outcomes. We show that IFN-III promotes a TH1 microenvironment through increased production of IL-12p70, IFN-γ, and cytotoxic lymphocyte–recruiting chemokines. Last, we showed that engagement of TLR3 is a therapeutic strategy to induce IFN-III production by tumor-associated cDC1. These data provide insight into potential IFN- or cDC1-targeting antitumor therapies.

scholarly journals Delta-secretase cleavage of Tau mediates its pathology and propagation in Alzheimer’s disease

2020 ◽  
Vol 52 (8) ◽  
pp. 1275-1287
Author(s):  
Seong Su Kang ◽  
Eun Hee Ahn ◽  
Keqiang Ye
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Strategy ◽  
Senile Plaques ◽  
Tau Pathology ◽  
Disease Modifying ◽  
Tau Aggregation ◽  
The Brain ◽  
Insight Into

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease with age as a major risk factor. AD is the most common dementia with abnormal structures, including extracellular senile plaques and intraneuronal neurofibrillary tangles, as key neuropathologic hallmarks. The early feature of AD pathology is degeneration of the locus coeruleus (LC), which is the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD. The spread of Tau deposits is first initiated in the LC and is transported in a stepwise manner from the entorhinal cortex to the hippocampus and then to associative regions of the neocortex as the disease progresses. Most recently, we reported that the NE metabolite DOPEGAL activates delta-secretase (AEP, asparagine endopeptidase) and triggers pathological Tau aggregation in the LC, providing molecular insight into why LC neurons are selectively vulnerable to developing early Tau pathology and degenerating later in the disease and how δ-secretase mediates the spread of Tau pathology to the rest of the brain. This review summarizes our current understanding of the crucial role of δ-secretase in driving and spreading AD pathologies by cleaving multiple critical players, including APP and Tau, supporting that blockade of δ-secretase may provide an innovative disease-modifying therapeutic strategy for treating AD.

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