scholarly journals Effects of Curcumin Analogues DMC and EF24 in Combination with the Cytokine TRAIL against Kidney Cancer

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6302
Author(s):  
Verónica Ibáñez Gaspar ◽  
Jasmin McCaul ◽  
Hilary Cassidy ◽  
Craig Slattery ◽  
Tara McMorrow
Keyword(s):  
Cell Viability ◽  
Natural Compound ◽  
Therapeutic Potential ◽  
Death Receptor ◽  
Therapeutic Effects ◽  
Curcumin Analogues ◽  
Anticancer Effects ◽  
Wide Range ◽  
Trail Resistance ◽  
Death Receptor 4

The natural compound curcumin has been shown to have therapeutic potential against a wide range of diseases such as cancer. Curcumin reduces cell viability of renal cell carcinoma (RCC) cells when combined with TNF-related apoptosis-inducing ligand (TRAIL), a cytokine that specifically targets cancer cells, by helping overcome TRAIL resistance. However, the therapeutic effects of curcumin are limited by its low bioavailability. Similar compounds to curcumin with higher bioavailability, such as demethoxycurcumin (DMC) and 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), can potentially have similar anticancer effects and show a similar synergy with TRAIL, thus reducing RCC viability. This study aims to show the effects of DMC and EF24 in combination with TRAIL at reducing ACHN cell viability and ACHN cell migration. It also shows the changes in death receptor 4 (DR4) expression after treatment with these compounds individually and in combination with TRAIL, which can play a role in their mechanism of action.

scholarly journals HuR Contributes to TRAIL Resistance by Restricting Death Receptor 4 Expression in Pancreatic Cancer Cells

2016 ◽  
Vol 14 (7) ◽  
pp. 599-611 ◽  
Author(s):  
Carmella Romeo ◽  
Matthew C. Weber ◽  
Mahsa Zarei ◽  
Danielle DeCicco ◽  
Saswati N. Chand ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Death Receptor ◽  
Pancreatic Cancer Cells ◽  
Trail Resistance ◽  
Death Receptor 4

scholarly journals Psychedelics and Other Psychoplastogens for Treating Mental Illness

2021 ◽  
Vol 12 ◽  
Author(s):  
Maxemiliano V. Vargas ◽  
Retsina Meyer ◽  
Arabo A. Avanes ◽  
Mark Rus ◽  
David E. Olson
Keyword(s):  
Mental Illness ◽  
Neural Plasticity ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Brain Disorders ◽  
Post Traumatic Stress ◽  
Neuropsychiatric Diseases ◽  
Wide Range ◽  
One Step ◽  
Post Traumatic

Psychedelics have inspired new hope for treating brain disorders, as they seem to be unlike any treatments currently available. Not only do they produce sustained therapeutic effects following a single administration, they also appear to have broad therapeutic potential, demonstrating efficacy for treating depression, post-traumatic stress disorder (PTSD), anxiety disorders, substance abuse disorder, and alcohol use disorder, among others. Psychedelics belong to a more general class of compounds known as psychoplastogens, which robustly promote structural and functional neural plasticity in key circuits relevant to brain health. Here we discuss the importance of structural plasticity in the treatment of neuropsychiatric diseases, as well as the evidence demonstrating that psychedelics are among the most effective chemical modulators of neural plasticity studied to date. Furthermore, we provide a theoretical framework with the potential to explain why psychedelic compounds produce long-lasting therapeutic effects across a wide range of brain disorders. Despite their promise as broadly efficacious neurotherapeutics, there are several issues associated with psychedelic-based medicines that drastically limit their clinical scalability. We discuss these challenges and how they might be overcome through the development of non-hallucinogenic psychoplastogens. The clinical use of psychedelics and other psychoplastogenic compounds marks a paradigm shift in neuropsychiatry toward therapeutic approaches relying on the selective modulation of neural circuits with small molecule drugs. Psychoplastogen research brings us one step closer to actually curing mental illness by rectifying the underlying pathophysiology of disorders like depression, moving beyond simply treating disease symptoms. However, determining how to most effectively deploy psychoplastogenic medicines at scale will be an important consideration as the field moves forward.

scholarly journals Potential Therapeutic Effects of Natural Plant Compounds in Kidney Disease

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6096
Author(s):  
Lorena Avila-Carrasco ◽  
Elda Araceli García-Mayorga ◽  
Daisy L. Díaz-Avila ◽  
Idalia Garza-Veloz ◽  
Margarita L Martinez-Fierro ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Clinical Studies ◽  
Renal Damage ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Protective Agent ◽  
Natural Plant ◽  
Wide Range ◽  
The Impact ◽  
Plant Compounds

Background: The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide range of diseases are the uncontrolled inflammatory reactions that promote fibrosis, oxidative reactions, and other alterations. Natural plant compounds (NPCs) are bioactive elements obtained from natural sources that can regulate physiological processes. Inflammation is recognized as an important factor in the development and evolution of chronic renal damage. Consequently, any compound able to modulate inflammation or inflammation-related processes can be thought of as a renal protective agent and/or a potential treatment tool for controlling renal damage. The objective of this research was to review the beneficial effects of bioactive natural compounds on kidney damage to reveal their efficacy as demonstrated in clinical studies. Methods: This systematic review is based on relevant studies focused on the impact of NPCs with therapeutic potential for kidney disease treatment in humans. Results: Clinical studies have evaluated NPCs as a different way to treat or prevent renal damage and appear to show some benefits in improving OS, inflammation, and antioxidant capacity, therefore making them promising therapeutic tools to reduce or prevent the onset and progression of KD pathogenesis. Conclusions: This review shows the promising clinical properties of NPC in KD therapy. However, more robust clinical trials are needed to establish their safety and therapeutic effects in the area of renal damage.

scholarly journals Actions and Therapeutic Potential of Madecassoside and Other Major Constituents of Centella asiatica: A Review

2021 ◽  
Vol 11 (18) ◽  
pp. 8475
Author(s):  
Swee Ching Tan ◽  
Subrat Kumar Bhattamisra ◽  
Dinesh Kumar Chellappan ◽  
Mayuren Candasamy
Keyword(s):  
Clinical Studies ◽  
Therapeutic Potential ◽  
Folk Medicine ◽  
Centella Asiatica ◽  
Therapeutic Effects ◽  
Active Constituents ◽  
Wide Range ◽  
The Subject ◽  
Therapeutic Properties ◽  
Skin Conditions

Centella asiatica is a popular herb well-known for its wide range of therapeutic effects and its use as a folk medicine for many years. Its therapeutic properties have been well correlated with the presence of asiaticoside, madecassoside, asiatic and madecassic acids, the pentacyclic triterpenes. The herb has been extensively known to treat skin conditions; nevertheless, several pre-clinical and clinical studies have scientifically demonstrated its effectiveness in other disorders. Among the active constituents that have been identified in Centella asiatica, madecassoside has been the subject of only a relatively small number of scientific reports. Therefore, this review, while including other major constituents of this plant, focuses on the therapeutic potential, pharmacokinetics and toxicity of madecassoside.

scholarly journals Overcoming TRAIL Resistance for Glioblastoma Treatment

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 572
Author(s):  
Longfei Deng ◽  
Xuan Zhai ◽  
Ping Liang ◽  
Hongjuan Cui
Keyword(s):  
Therapeutic Potential ◽  
Death Receptor ◽  
Apoptosis Pathway ◽  
Reasonable Expectation ◽  
The Status ◽  
Extrinsic Apoptosis ◽  
Trail Resistance ◽  
Induced Apoptosis ◽  
Trail Death Receptor ◽  
Necrosis Factor

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) shows a promising therapeutic potential in cancer treatment as it exclusively causes apoptosis in a broad spectrum of cancer cells through triggering the extrinsic apoptosis pathway via binding to cognate death receptors, with negligible toxicity in normal cells. However, most cancers, including glioblastoma multiforme (GBM), display TRAIL resistance, hindering its application in clinical practice. Recent studies have unraveled novel mechanisms in regulating TRAIL-induced apoptosis in GBM and sought effective combinatorial modalities to sensitize GBM to TRAIL treatment, establishing pre-clinical foundations and the reasonable expectation that the TRAIL/TRAIL death receptor axis could be harnessed to treat GBM. In this review, we will revisit the status quo of the mechanisms of TRAIL resistance and emerging strategies for sensitizing GBM to TRAIL-induced apoptosis and also discuss opportunities of TRAIL-based combinatorial therapies in future clinical use for GBM treatment.

scholarly journals Synthesis and Characterization of Dose-Dependent Antioxidants and Antimicrobial Activity of Phloretin Loaded PLGA Nanoparticles

2021 ◽  
Vol 12 (3) ◽  
pp. 3076-3089
Keyword(s):  
Antimicrobial Activity ◽  
Zeta Potential ◽  
Therapeutic Potential ◽  
Polymeric Nanoparticles ◽  
Radical Scavenging Activity ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Antibacterial Properties ◽  
Therapeutic Effects ◽  
Wide Range

This aim of the study combines and differentiates Phloretin-encapsulated PLGA (poly (dl-lactide-coglycolide) nanoparticles and assesses their antioxidant and antibacterial properties. Phloretin is a possible active ingredient with a wide range of therapeutic effects. The process of emulsification was used to make nanoparticles. Physicochemical properties were measured by Particle size, polydispersity index, and zeta-potential investigated by dynamic light scattering (DLS), X-ray diffraction, FTIR, TEM, and AFM. FTIR results proven that phloretin formulated PLGA NPs exhibited functional groups. The Zeta potential size analyzer results of the optimal NPs size were 98.7 nm. The crystallinity nature peaks related to Phloretin-PLGA NPs were confirmed by XRD. Antioxidant properties of free and encapsulated nanoparticles were determined by DP, method. Relatively small polymeric nanoparticles were obtained containing phloretin. DPPH radical scavenging activity of the nanoparticles was found to be 71% at a 1 mg/ml concentration. It also had antibacterial properties when examined using the good diffusion approach against Negative species. In conclusion, our findings show that encapsulated PLGA phloretin nanoparticles with continuous release properties retain antioxidant and antimicrobial activity, implying therapeutic potential.

scholarly journals The Multifaceted Role of Curcumin in Advanced Nanocurcumin Form in the Treatment and Management of Chronic Disorders

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7109
Author(s):  
Priti Tagde ◽  
Pooja Tagde ◽  
Fahadul Islam ◽  
Sandeep Tagde ◽  
Muddaser Shah ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Review Article ◽  
Biological Pathways ◽  
Therapeutic Benefits ◽  
Anticancer Effects ◽  
Wide Range ◽  
Cellular Permeability ◽  
Chronic Disorders ◽  
Viable Method

Curcumin is the primary polyphenol in turmeric’s curcuminoid class. It has a wide range of therapeutic applications, such as anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers, but has poor solubility and low bioavailability. Objective: To improve curcumin’s bioavailability, plasma concentration, and cellular permeability processes. The nanocurcumin approach over curcumin has been proven appropriate for encapsulating or loading curcumin (nanocurcumin) to increase its therapeutic potential. Conclusion: Though incorporating curcumin into nanocurcumin form may be a viable method for overcoming its intrinsic limitations, and there are reasonable concerns regarding its toxicological safety once it enters biological pathways. This review article mainly highlights the therapeutic benefits of nanocurcumin over curcumin.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

Isoform-Selective PI3K Inhibitors for Various Diseases

2020 ◽  
Vol 20 (12) ◽  
pp. 1074-1092 ◽  
Author(s):  
Rammohan R.Y. Bheemanaboina
Keyword(s):  
Intracellular Signaling ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Type I ◽  
Selective Inhibitors ◽  
Pi3k Inhibitors ◽  
Wide Range ◽  
Lipid Kinases ◽  
Isoform Selectivity

Phosphoinositide 3-kinases (PI3Ks) are a family of ubiquitously distributed lipid kinases that control a wide variety of intracellular signaling pathways. Over the years, PI3K has emerged as an attractive target for the development of novel pharmaceuticals to treat cancer and various other diseases. In the last five years, four of the PI3K inhibitors viz. Idelalisib, Copanlisib, Duvelisib, and Alpelisib were approved by the FDA for the treatment of different types of cancer and several other PI3K inhibitors are currently under active clinical development. So far clinical candidates are non-selective kinase inhibitors with various off-target liabilities due to cross-reactivities. Hence, there is a need for the discovery of isoform-selective inhibitors with improved efficacy and fewer side-effects. The development of isoform-selective inhibitors is essential to reveal the unique functions of each isoform and its corresponding therapeutic potential. Although the clinical effect and relative benefit of pan and isoformselective inhibition will ultimately be determined, with the development of drug resistance and the demand for next-generation inhibitors, it will continue to be of great significance to understand the potential mechanism of isoform-selectivity. Because of the important role of type I PI3K family members in various pathophysiological processes, isoform-selective PI3K inhibitors may ultimately have considerable efficacy in a wide range of human diseases. This review summarizes the progress of isoformselective PI3K inhibitors in preclinical and early clinical studies for anticancer and other various diseases.

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