scholarly journals Polyphenols Targeting MAPK Mediated Oxidative Stress and Inflammation in Rheumatoid Arthritis

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6570
Author(s):  
Tapan Behl ◽  
Tanuj Upadhyay ◽  
Sukhbir Singh ◽  
Sridevi Chigurupati ◽  
Amal M. Alsubayiel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Bone Erosion ◽  
Mapk Signaling ◽  
Future Research ◽  
Pathophysiological Mechanism ◽  
Critical Function ◽  
Research Perspectives

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disorder, predominantly symmetric, which causes joint inflammation, cartilage degeneration and bone erosion, resulting in deformity and the loss of physical function. Although the management of RA has steadily improved, the pathophysiological mechanism is incompletely elucidated, and therapeutic options are still limited. Due to shortcomings in the efficacy or safety profiles of conventional RA therapies, therapeutic alternatives have been considered. Therefore, natural extracts containing polyphenolic compounds can become promising adjuvant agents for RA global management, due to their antioxidant, anti-inflammatory and apoptotic properties. Polyphenols can regulate intracellular signaling pathways in RA and can generate different immune responses through some key factors (i.e., MAPK, interleukins (ILs 1 and 6), tumor necrosis factor (TNF), nuclear factor light k chain promoter of activated receptor (NF-κB), and c-Jun N-terminal kinases (JNK)). The critical function of the Toll like-receptor (TLR)-dependent mitogen-activating protein kinase (MAPK) signaling pathway in mediating the pathogenic characteristics of RA has been briefly discussed. Oxidative stress can trigger a change in transcription factors, which leads to the different expression of some genes involved in the inflammatory process. This review aims to provide a comprehensive perspective on the efficacy of polyphenols in mitigating RA by inhibiting signaling pathways, suggesting future research perspectives in order to validate their use.

scholarly journals Management of Rheumatoid Arthritis: An Overview

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2857
Author(s):  
Andrei-Flavius Radu ◽  
Simona Gabriela Bungau
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Status ◽  
Future Research ◽  
Unknown Etiology ◽  
Pathophysiological Mechanism ◽  
Efficacy And Safety ◽  
Systemic Complications ◽  
Synthetic Drugs ◽  
Research Perspectives ◽  
Medical Advances

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease of unknown etiology, primarily affecting the joints, then extra-articular manifestations can occur. Due to its complexity, which is based on an incompletely elucidated pathophysiological mechanism, good RA management requires a multidisciplinary approach. The clinical status of RA patients has improved in recent years due to medical advances in diagnosis and treatment, that have made it possible to reduce disease activity and prevent systemic complications. The most promising results were obtained by developing disease-modifying anti-rheumatic drugs (DMARDs), the class to which conventional synthetic, biologic, and targeted synthetic drugs belong. Furthermore, ongoing drug development has led to obtaining molecules with improved efficacy and safety profiles, but further research is needed until RA turns into a curable pathology. In the present work, we offer a comprehensive perspective on the management of RA, by centralizing the existing data provided by significant literature, emphasizing the importance of an early and accurate diagnosis associated with optimal personalized treatment in order to achieve better outcomes for RA patients. In addition, this study suggests future research perspectives in the treatment of RA that could lead to higher efficacy and safety profiles and lower financial costs.

scholarly journals Diquat Determines a Deregulation of lncRNA and mRNA Expression in the Liver of Postweaned Piglets

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jin Wang ◽  
Zhi-xin Li ◽  
Dan-dan Yang ◽  
Pei-qi Liu ◽  
Zhi-qiang Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Performance ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Reduction Process ◽  
Future Research ◽  
Control Group ◽  
Oxidoreductase Activity ◽  
Go Terms ◽  
Porcine Hepatocytes

Oxidative stress is detrimental to animals and can depress the growth performance and regulate the gene expression of animals. However, it remains unclear how oxidative stress regulates the expression of long noncoding RNAs (lncRNAs) and mRNAs. Therefore, the purpose of this article was to explore the profiles of lncRNAs and mRNAs in the liver of piglets under oxidative stress. Here, we constructed a piglet oxidative stress model induced by diquat and evaluated the effects of oxidative stress on the growth performance and antioxidant enzyme activity of piglets. We also used RNA-Seq to examine the global expression of lncRNAs and mRNAs in piglets under oxidative stress. The targets of lncRNAs and mRNAs were enriched in gene ontology (GO) terms and signaling pathways. The results show that the growth performance and activities of antioxidant enzymes were decreased in piglets under oxidative stress. Moreover, eight lncRNAs (6 upregulated and 2 downregulated) and 30 mRNAs (8 upregulated and 22 downregulated) were differentially expressed in the oxidative stress group of piglets compared to the negative control group. According to biological processes in enriched GO terms, the oxoacid metabolic process, intramolecular oxidoreductase activity, and oxidation-reduction process play important roles in oxidative stress. Pathway analysis showed that the signaling pathways involved in insulin and glucose metabolism had a close relationship with oxidative stress. Furtherin vitroexperiments showed that the expression of the upregulated geneGNMTwas significantly increased in primary porcine hepatocytes after diquat stimulation. In contrast, the level of the downregulated geneGCKwas significantly decreased at 12 h in primary porcine hepatocytes after diquat stimulation. Our results expand our knowledge of the lncRNAs and mRNAs transcribed in the livers of piglets under oxidative stress and provide a basis for future research on the molecular mechanisms mediating oxidative stress and tissue damage.

scholarly journals Nanodelivery Systems Targeting Epidermal Growth Factor Receptors for Glioma Management

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1198
Author(s):  
Sathishbabu Paranthaman ◽  
Meghana Goravinahalli Shivananjegowda ◽  
Manohar Mahadev ◽  
Afrasim Moin ◽  
Shivakumar Hagalavadi Nanjappa ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Protein Kinase ◽  
Cell Surface ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Future Research ◽  
Extensive Literature ◽  
Egfr Tkis

A paradigm shift in treating the most aggressive and malignant form of glioma is continuously evolving; however, these strategies do not provide a better life and survival index. Currently, neurosurgical debulking, radiotherapy, and chemotherapy are the treatment options available for glioma, but these are non-specific in action. Patients invariably develop resistance to these therapies, leading to recurrence and death. Receptor Tyrosine Kinases (RTKs) are among the most common cell surface proteins in glioma and play a significant role in malignant progression; thus, these are currently being explored as therapeutic targets. RTKs belong to the family of cell surface receptors that are activated by ligands which in turn activates two major downstream signaling pathways via Rapidly Accelerating Sarcoma/mitogen activated protein kinase/extracellular-signal-regulated kinase (Ras/MAPK/ERK) and phosphatidylinositol 3-kinase/a serine/threonine protein kinase/mammalian target of rapamycin (PI3K/AKT/mTOR). These pathways are critically involved in regulating cell proliferation, invasion, metabolism, autophagy, and apoptosis. Dysregulation in these pathways results in uncontrolled glioma cell proliferation, invasion, angiogenesis, and cancer progression. Thus, RTK pathways are considered a potential target in glioma management. This review summarizes the possible risk factors involved in the growth of glioblastoma (GBM). The role of RTKs inhibitors (TKIs) and the intracellular signaling pathways involved, small molecules under clinical trials, and the updates were discussed. We have also compiled information on the outcomes from the various endothelial growth factor receptor (EGFR)–TKIs-based nanoformulations from the preclinical and clinical points of view. Aided by an extensive literature search, we propose the challenges and potential opportunities for future research on EGFR–TKIs-based nanodelivery systems.

scholarly journals Myricetin Protects Cells against Oxidative Stress-Induced Apoptosis via Regulation of PI3K/Akt and MAPK Signaling Pathways

2010 ◽  
Vol 11 (11) ◽  
pp. 4348-4360 ◽  
Author(s):  
Kyoung Ah Kang ◽  
Zhi Hong Wang ◽  
Rui Zhang ◽  
Mei Jing Piao ◽  
Ki Cheon Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Induced Apoptosis ◽  
Mapk Signaling Pathways
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