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.

Novel archetype in cancer therapeutics: exploring prospective of phytonanocarriers.

This paper reports various types of cancer, their incidence, and prevalence all over the globe. Along with the discovery of novel natural drugs for cancer treatment, these present a promising option which are eco-friendly, safe, and provide better acceptability in comparison to synthetic agents that carries multiple side effects. This paper provides an idea about various nanocarriers and phytochemicals, along with how their solubility and bioavailability can be enhanced in nanocarrier system. This report combines the data from various literature available on public domain including PubMed on research articles, reviews, and along with report from various national and international sites. Specialized metabolites (polyphenols, alkaloids, and steroids etc) from medicinal plants are promising alternatives to existing drugs. Studies have suggested that the treatment of cancer using plant products could be an alternative and a safe option. Studies have shown with the several cell lines as well as animal models, that phytomolecules are important in preventing/treating cancer. Phytochemicals often outperform chemical treatments by modulating a diverse array of cellular signaling pathways, promoting cell cycle arrest, apoptosis activation, and metastatic suppression, among others. However, limited water solubility, bioavailability, and cell penetration limit their potential clinical manifestations. The development of plant extract loaded nanostructures, rendering improved specificity and efficacy at lower concentrations could prove effective. Nanocarriers, such as liposomes, nanostructured lipids, polymers, and metal nanoparticles, have been tested for the delivery of plant products with enhanced effects. Recent advances have achieved improvement in the the stability, solubility, bioavailability, circulation time, and target specificity by nanostructure-mediated delivery of phytochemicals. Nanoparticles have been considered and attempted as a novel, targeted, and safe option. Newer approaches such as phyto-nanocarriers with carbohydrates, lignin, and polymers have been considered even more selective and effective modes of drug delivery in biomedical or diagnostic applications.

A lineage-specific requirement for YY1 Polycomb Group protein function in early T cell development.

Yin Yang 1 (YY1) is a ubiquitous transcription factor and mammalian Polycomb Group protein (PcG) with important functions for regulating lymphocyte development and stem cell self-renewal. YY1 mediates stable PcG-dependent transcriptional repression via recruitment of PcG proteins that result in histone modifications. Many questions remain unanswered regarding how cell- and tissue-specificity is achieved by PcG proteins. Here, we demonstrate that a conditional knockout of Yy1 in the hematopoietic system results in an early T cell developmental blockage at the double negative (DN) 1 stage with reduced Notch1 signaling. There is a lineage-specific requirement for YY1 PcG function. YY1 PcG domain is required for T and B cell development but not necessary for myeloid cells. YY1 functions in early T cell development are multicomponent and involve both PcG-dependent and -independent regulations. Although YY1 promotes early T cell survival through its PcG function, its function to promote the DN1-to-DN2 transition and Notch1 expression and signaling is independent of its PcG function. Our results reveal how a ubiquitously expressed PcG protein mediates lineage-specific and context-specific functions to control early T cell development.

Decompression retinochoroidopathy: a unique presentation post-trabeculectomy.

PURPOSE: To present a unique case of decompression retinochoroidopathy presenting with intraretinal, subretinal and preretinal hemorrhages. METHODS: A 65-year-old hypertensive female presented with diminution of vision in right eye of 1-week duration. She had been a known case of primary open-angle glaucoma and had undergone trabeculectomy with mitomycin C in right eye 1 week back. Her day 1 postoperative intraocular pressure was 6 mmHg. Her left eye had undergone Ahmed glaucoma valve surgery for the same 2 years back. RESULT: Right eye vision at 1 week of presentation was 6/36, N36 and left eye hand movements. Both eyes were pseudophakic. Intraocular pressure in right eye was 35 mmHg with nonfunctional bleb and in left eye 15 mmHg. Right eye fundus shows multiple subretinal, intraretinal, preretinal and some white-centered blot hemorrhage in all the four quadrants including the posterior pole. Disk had glaucomatous cupping with no dilatation or tortuosity of retinal blood vessels. Left eye had total glaucomatous optic atrophy. CONCLUSION: Old hypertensive females may not tolerate hemodynamic changes in retinal and choroidal vasculature so well, and if the autoregulation of retinal capillaries and choriocapillaris fails because of IOP spikes or rise of IOP to high levels in a relatively short duration, sudden lowering of IOP after trabeculectomy may cause decompression retinopathy and choroidopathy.

Ceramic nanoparticles: Recompense, cellular uptake and toxicity concerns.

Over the past few years, nanoparticles and their role in drug delivery have been the centre of attraction as new drug delivery systems. Various forms of nanosystems have been designed, such as nanoclays, scaffolds and nanotubes, having numerous applications in areas such as drug loading, target cell uptake, bioassay and imaging. The present study discusses various types of nanoparticles, with special emphasis on ceramic nanocarriers. Ceramic materials have high mechanical strength, good body response and low or non-existing biodegradability. In this article, the various aspects concerning ceramic nanoparticles, such as their advantages over other systems, their cellular uptake and toxicity concerns are discussed in detail.

Iris intraocular foreign bodies: safe and successful removal through limbus.

Metallic iris intra ocular foreign body (IOFBs) with minimal ocular damage pose an interventional challenge. We report safe removal of metallic intraocular foreign bodies embedded on the iris, in three cases by use of intraocular magnets. Two eyes had a clear lens with best corrected visual acuity (BCVA) of 20/20, while the third eye had a BCVA of 20/200 with siderotic cataract. Ultrasound biomicroscopy confirmed the superficial impaction of IOFB into the iris. Foreign bodies were successfully removed via the limbal route with a 20 g intravitreal magnet atraumatically in all 3 cases with preservation of their pre-operative BCVA. Case series highlights the usefulness and safety of intraocular magnet for removal of metallic iris foreign bodies in selected cases. Prior ultrasound biomicroscopy to know the actual depth of penetration of IOFB into the iris and preoperative confirmation of magnetic property of IOFB are essential.