Role and uptake of metal-based nanoconstructs as targeted therapeutic carriers for rheumatoid arthritis.

Rheumatoid Arthritis (RA) is a chronic autoimmune systemic inflammatory disease that affects the joints and other vital organs and diminishes the quality of life. The current developments and innovative treatment options have significantly slowed disease progression and improved their quality of life. Medicaments can be delivered to the inflamed synovium via nanoparticle systems, minimizing systemic and undesirable side effects. Numerous nanoparticles such as polymeric, liposomal, and metallic nanoparticles reported are impending as a good carrier with therapeutic properties. Other issues to be considered along are nontoxicity, nanosize, charge, optical property, and ease of high surface functionalization that make them suitable carriers for drug delivery. Metallic nanoparticles (MNPs) (such as silver, gold, zinc, iron, titanium oxide, and selenium) not only act as good carrier with desired optical property, and high surface modification ability but also have their own therapeutical potential such as anti-oxidant, anti-inflammatory, and anti-arthritic properties, making them one of the most promising options for RA treatment. Regardless, cellular uptake of MNPs is one of the most significant criterions for targeting the medication. This paper discusses the numerous interactions of nanoparticles with cells, as well as cellular uptake of NPs. This review provides the mechanistic overview on MNPs involved in RA therapies and regulation anti-arthritis response such as ability to reduce oxidative stress, suppressing the release of proinflammatory cytokines and expression of LPS induced COX-2, and modulation of MAPK and PI3K pathways in Kuppfer cells and hepatic stellate cells. Despite of that MNPs have also ability to regulates enzymes like glutathione peroxidases (GPxs), thioredoxin reductases (TrxRs) and act as an anti-inflammatory agent.

Targeting Pathways and Integrated Approaches to Treat Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic symmetrical systemic disorder that not only affects joints but also other organs such as heart, lungs, kidney, and liver. Approximately there is 0.5%-1% of the total population affected by RA. RA pathogenesis still remains unclear due to which its appropriate treatment is a challenge. Further, multitudes of factors have been reported to affect its progression i.e. genetic factor, environmental factor, immune factor, and oxidative factor. Therapeutic approaches available for the treatment of RA include NSAIDs, DMARDs, enzymatic, hormonal, and gene therapies. But most of them provide the symptomatic relief without treating the core of the disease. This makes it obligatory to explore and reach the molecular targets for cure and long-term relief from RA. Herein, we attempt to provide extensive overlay of the new targets for RA treatment such as signaling pathways, proteins, and receptors affecting the progression of the disease and its severity. Precise modification in these targets such as suppressing the notch signaling pathway, SIRT 3 protein, Sphingosine-1-phosphate receptor and stimulating the neuronal signals particularly efferent vagus nerve and SIRT 1 protein may offer long term relief and potentially diminish the chronicity. To target or alter the novel molecules and signaling pathway a specific delivery system is required such as liposome, nanoparticles and micelles and many more. Present review paper discusses in detail about novel targets and delivery systems for treating RA.

Plant-Based Approaches for Rheumatoid Arthritis Regulation: Mechanistic Insights on Pathogenesis, Molecular Pathways, and Delivery Systems.

Rheumatoid arthritis (RA) is classified as a chronic inflammatory autoimmune disorder, associated with a varied range of immunological changes, synovial hyperplasia, cartilage destructions, as well as bone erosion. The infiltration of immune-modulatory cells and excessive release of proinflammatory chemokines, cytokines, and growth factors into the inflamed regions are key molecules involved in the progression of RA. Even though many conventional drugs are suggested by a medical practitioner such as DMARDs, NSAIDs, glucocorticoids, etc., to treat RA, but have allied with various side effects. Thus, alternative therapeutics in the form of herbal therapy or phytomedicine has been increasingly explored for this inflammatory disorder of joints. Herbal interventions contribute substantial therapeutic benefits including accessibility, less or no toxicity and affordability. But the major challenge with these natural actives is the need of a tailored approach for treating inflamed tissues by delivering these bioactive agentsat an appropriate dose within the treatment regimen for an extended periodof time. Drug incorporated with wide range of delivery systems such as liposomes, nanoparticles, polymeric micelles, and other nano-vehicles have been developed to achieve this goal. Thus, inclinations of modern treatment are persuaded on the way to herbal therapy or phytomedicines in combination with novel carriers is an alternative approach with less adverse effects. The present review further summarizes the significanceof use of phytocompounds, their target molecules/pathways and, toxicity and challenges associated with phytomolecule-based nanoformulations.

A Review on Molecular Docking As an Interpretative Tool for Molecular Targets in Disease Management.

One of the most often utilized methods for drug discovery is molecular docking. With docking, one may discover new therapeutically relevant molecules by targeting the molecule and predicting the target-ligand interactions as well as different conformation of ligand at various positions. The prediction signifies the effectiveness of the molecule or the developed molecule having different affinity with target. Drug discovery plays an important role in the development of a new drug molecule of different moiety attached to it, which leads us in the management of several diseases. In silico approach led us to identification of numerous diseases caused by virus, fungi, bacteria, protozoa, and other microorganisms that affect human health. By means of computational approach, we can categorize disease symptoms and use the drugs available for such types of warning signs. After the docking process, molecular dynamics computational technique helps in the simulation of the physical movement of atoms and molecules for a fixed period of time, giving a view of the dynamic evaluation of the system. This review is an attempt to illustrate the role of molecular docking in drug development.

Mechanistic insight on the role of iRhom2-TNF-α-BAFF signaling pathway in various autoimmune disorders.

iRhom2 is a crucial cofactor involved in upregulation of TNF receptors (TNFRs) and the pro-inflammatory cytokine tumor necrosis factor (TNF-) from the cell surface by ADAM17. Tumor necrosis factor- α converting enzyme (TACE) is another name given to ADAM17. Many membrane attached biologically active molecules are cleaved by this enzyme which includes TNFRs and the pro-inflammatory cytokine tumor necrosis factor- α. The TNF receptors are of two types TNFR1 and TNFR2. iRhom2 belongs to the pseudo-protease class of rhomboid family, its abundance is observed in the immune cells. Biological activity of ADAM17 is affected in multiple levels by the iRhom2. ADAM17 is trafficked into the Golgi apparatus by the action of iRhom2, where it gets matured proteolytically and is stimulated to perform its function on the cell surface. This process of activation of ADAM17 results in the protection of the organism from the cascade of inflammatory reactions, as this activation blocks the TNF- α mediated secretion responsible for inflammatory responses produced. Present paper illustrates about the iRhom2-TNF-α-BAFF signaling pathway and its correlation with several autoimmune disorders such as Rheumatoid Arthritis, Systemic Lupus Erythematosus, Hemophilia Arthropathy, Alzheimer's disease and Tylosis with esophageal cancer etc.

Mechanistic prospective and pharmacological attributes of quercetin in attenuation of different types of arthritis.

Arthritis is a frequent autoimmune disease with undefined etiology and pathogenesis. Scientific community constantly fascinating quercetin (QUR), as it is the best-known flavonoid among others for curative and preventive properties against a wide range of diseases. Due to its multifaceted activities, the implementation of QUR against various types of arthritis namely, rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis (GA) and psoriotic arthritis (PsA) has greatly increased in recent years. Many research evidenced that QUR regulates a wide range of pathways for instance NF-κB, MAK, Wnt/ß-catenine, Notch, etc., that are majorly associated with the inflammatory mechanisms. Besides, the bioavailability of QUR is a major constrain to its therapeutic potential, and drug delivery techniques have experienced significant development to overcome the problem of its limited application. Hence, this review compiled the cutting-edge experiments on versatile effects of QUR on inflammatory diseases like RA, OA, GA and PsA, sources and bioavailability, therapeutic challenges, pharmacokinetics, clinical studies as well as toxicological impacts. The use of QUR in a health context would offer a tearing and potential therapeutic method, supporting the advancement of public health, particularly, of arthritic patients worldwide.

Novel Biotherapeutics Targeting Biomolecular and Cellular Approaches in Diabetic Wound Healing.

Wound healing responses play a major role in chronic inflammation, which affects millions of people around the world. One of the daunting tasks of creating a wound-healing drug is finding equilibrium in the inflammatory cascade. In this study, the molecular and cellular mechanisms to regulate wound healing are explained, and recent research is addressed that demonstrates the molecular and cellular events during diabetic wound healing. Moreover, a range of factors or agents that facilitate wound healing have also been investigated as possible targets for successful treatment. It also summarises the various advances in research findings that have revealed promising molecular targets in the fields of therapy and diagnosis of cellular physiology and pathology of wound healing, such as neuropeptides, substance P, T cell immune response cDNA 7, miRNA, and treprostinil growth factors such as fibroblast growth factor, including thymosin beta 4, and immunomodulators as major therapeutic targets.