Efficacy of phyto-therapeutics in allergic rhinitis: A review

Allergic rhinitis (AR) or hay fever is the most common symptomatic allergic disorder triggered by allergen and if it remains undiagnosed, can adversely impact the general well-being. The ailment is characterized by an exaggerated immune response to environmental triggers including pollen, moulds, ragweed, dirt mites, dust, etc. within the nasal mucosa, ultimately leading to gene environment interaction which elevate the IgE level in the nasal mucosa, and ultimately infection of the nasal cavity. The major signs and symptoms of AR include rhinorrhea, sneezing, eye itching, postnasal drip, cough, nasal obstruction, and fatigue due to nasal discomfort. Various studies reported 20-30% occurrence of the disease and majority of them are inclined towards allopathic medication for instant relief. Since these drugs lead to unenviable side effects in the long term, it is of utmost importance to search for alternative mode of medication with lower side-effects. The use of traditional medication in the form of various herbal plants and their mixture have proved to be effective in the management of symptoms for asthma and AR. Their efficiencies have been restrained successfully in various reports. It has been proven that herbal medicines are safe to use and thus have rendered a vast contribution to the treatment of allergic rhinitis. Hence, the present review is aimed to discuss the efficacy and protection provided by diverse herbal drugs in the management of AR

Nuclear deubiquitination in the spotlight : the multifaceted nature of USP7 biology in disease

Ubiquitination is a versatile and tightly regulated post-translational protein modification with many distinct outcomes affecting protein stability, localization, interactions, and activity. Ubiquitin chain linkages anchored on substrates can be further modified by additional post-translational modifications, including phosphorylation and SUMOylation. Deubiquitinases (DUBs) reverse these ubiquitin marks with matched levels of precision. Over hundred known DUBs regulate a wide variety of cellular events. In this review, we focus on ubiquitin-specific protease 7 (USP7, also known as herpesvirus-associated ubiquitin-specific protease, or HAUSP) as one of the best studied, disease-associated DUBs. By highlighting the functions of USP7, particularly in the nucleus, and the emergence of the newest generation of USP7 inhibitors, we illustrate the importance of individual DUBs in the nucleus, and the therapeutic prospects of DUB targeting in human disease

Novel NADPH Oxidase-2 Inhibitors as Potential Anti-Inflammatory and Neuroprotective Agents

A family of seven NADPH oxidase enzymes (Nox1-5, Duox1-2) has been implicated in a variety of diseases, including inflammatory lung diseases, neurodegenerative diseases, cardiovascular diseases, and cancer. Here, we report the results of our studies aimed at developing novel brain-permeable Nox2 inhibitors with potential application as neuroprotective agents. Using cell-based assays, we identified a novel Nox2 inhibitor, TG15-132, that prevents PMA-stimulated oxygen consumption and reactive oxygen species (superoxide radical anion and hydrogen peroxide) formation upon acute treatment in differentiated HL60 cells. Long-term treatment with TG15-132 attenuates the induction of genes encoding Nox2 subunits, several inflammatory cytokines, and iNOS in differentiated THP-1 cells. Moreover, TG15-132 shows a relatively long plasma half-life (5.6 h) and excellent brain permeability, with a brain-to-plasma ratio (>5-fold) in rodent models. Additionally, TG15-132 does not cause any toxic effects on vital organs or blood biomarkers of toxicity in mice upon chronic dosing for seven days. We propose that TG15-132 may be used as a Nox2 inhibitor and a potential neuroprotective agent, with possible further structural modifications to increase its potency

Pharmacological antagonism of EP2 receptor does not modify basal cardiovascular and respiratory function, blood cell counts, and bone morphology in animal models.

The EP2 receptor has emerged as a therapeutic target with exacerbating role in disease pathology for a variety of peripheral and central nervous system disorders. We and others have recently demonstrated beneficial effects of EP2 antagonists in preclinical models of neuroinflammation and peripheral inflammation. However, it was earlier reported that mice with global EP2 knockout (KO) display adverse phenotypes on fertility and blood pressure. Other studies indicated that EP2 activation with an agonist has a beneficial effect of healing fractured bone in animal models. These results impeded the development of EP2 antagonists, and EP2 antagonism as therapeutic strategy. To determine whether treatment with EP2 antagonist mimics the adverse phenotypes of the EP2 global KO mouse, we tested two EP2 antagonists TG11-77. HCl and TG6-10-1 in mice and rats while they are on normal or high-salt diet, and by two different administration protocols (acute and chronic). There were no adverse effects of the antagonists on systolic and diastolic blood pressure, heart rate, respiratory function in mice and rats regardless of rodents being on a regular or high salt diet. Furthermore, chronic exposure to TG11-77. HCl produced no adverse effects on blood cell counts, bone-volume and bone-mineral density in mice. Our findings argue against adverse effects on cardiovascular and respiratory systems, blood counts and bone structure in healthy rodents from the use of small molecule reversible antagonists for EP2, in contrast to the genetic ablation model. This study paves the way for advancing therapeutic applications of EP2 antagonists against diseases involving EP2 dysfunction

Electro-ionic control of surface plasmons in graphene-layered heterostructures

Precise control of light is indispensable to modern optical communication devices especially as the size of such devices approaches the subwavelength scale. Plasmonic devices are suitable for the development of these optical devices due to the extreme field confinement and its ability to be controlled by tuning the carrier density at the metal/dielectric interface. Here, an electro-ionic controlled plasmonic device consisting of Au/graphene/ion-gel is demonstrated as an optical switch, where an external electric field modulates the real part of the electrical conductivity. The graphene layer enhances charge penetration and charge separation at the Au/graphene interface resulting in an increased photoinduced voltage. The ion-gel immobilized on the Au/graphene further enables the electrical tunability of plasmons which modulates the intensity of the reflected laser light. This work paves the way for developing novel plasmonic electro-optic switches for potential applications such as integrated optical devices.Ministry of Education (MOE)National Research Foundation (NRF)J.Y.P. acknowledges NTU for the Research Student Scholarship and SC3DP which is supported by the National Research Foundation, Prime Minister’s Office, Singapore under its Medium-Sized Centre funding scheme. This work was supported in part by the Ministry of Education (MOE), Singapore - Academic Research Funding (AcRF) Tier 1 Grant RG192/17. R.M. and R.S.R. acknowledge Grants MOE2017- T2-2-129 and MOE2019-T2-1-058. M.B. acknowledges NTU for the NAP-SUG grant

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ABSTRACT Context Autoimmune pancreatitis is characterized by immune-mediated inflammation, prominent lymphocytic infiltration and fibrosis of pancreas. It accounts for 4.6-6% of chronic pancreatitis but only a few cases from India have been reported