- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Tryptophan and brain disorders
- HIV Research and Treatment
- Long-Term Effects of COVID-19
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Molecular Biology Techniques and Applications
- Single-cell and spatial transcriptomics
- Computational Drug Discovery Methods
- HIV/AIDS drug development and treatment
- Autophagy in Disease and Therapy
- HIV-related health complications and treatments
- Dysphagia Assessment and Management
- Neurogenetic and Muscular Disorders Research
- Cannabis and Cannabinoid Research
- Psychedelics and Drug Studies
- Phenothiazines and Benzothiazines Synthesis and Activities
- Medicinal Plants and Neuroprotection
- CRISPR and Genetic Engineering
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Quinazolinone synthesis and applications
- Luminescence and Fluorescent Materials
University of Nebraska Medical Center
2018-2025
Maharaja Sayajirao University of Baroda
2015-2018
Indian Institute of Information Technology Vadodara
2015-2016
A novel series of hybrid molecules were designed and synthesized by fusing the pharmacophoric features cholinesterase inhibitor donepezil diarylthiazole as potential multitarget-directed ligands for treatment Alzheimer’s disease (AD). The compounds showed significant in vitro anticholinesterase (anti-ChE) activity, most potent compound (44) among them showing highest activity (IC50 value 0.30 ± 0.01 μM) AChE (1.84 0.03 BuChE. Compound 44 mixed inhibition enzyme kinetic studies. Some...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by pathological deposition of misfolded self-protein amyloid beta (Aβ) which in kind facilitates tau aggregation and neurodegeneration. Neuroinflammation accepted as key driver caused innate microglia activation. Recently, adaptive immune alterations have been uncovered that begin early persist throughout the disease. How these occur whether they can be harnessed to halt progress unclear. We propose...
Abstract Background Regulatory T cells (Tregs) maintain immune tolerance. While Treg-mediated neuroprotective activities are now well-accepted, the lack of defined antigen specificity limits their therapeutic potential. This is notable for neurodegenerative diseases where cell access to injured brain regions required disease-specific targeting and improved outcomes. To address this need, amyloid-beta (Aβ) was conferred Treg responses by engineering receptor (TCR) specific Aβ (TCR A β ). The...
A barrier to HIV-1 cure rests in the persistence of proviral DNA infected CD4+ leukocytes. The high mutation rate leads viral diversity, immune evasion, and consequent antiretroviral drug resistance. While CRISPR-spCas9 can eliminate latent DNA, its efficacy is limited by HIV strain diversity precision target cell delivery.A library guide RNAs (gRNAs) designed disrupt five exons (tat1-2/rev1-2/gp41) was constructed. gRNAs were derived from a conseensus sequence transcriptional regulator tat...
Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of distress (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening disease 2019 (COVID-19) heralded by virus-induced activation mononuclear phagocytes (MPs; monocytes, macrophages, dendritic cells). MPs play substantial roles in aberrant secretory activities affecting profound systemic inflammation malfunctions. All follow presence...
A paradigm shift has emerged in Parkinson's disease (PD) highlighting the prominent role of CD4+ Tregs pathogenesis and treatment. Bench to bedside research, conducted by others our own laboratories, advanced a neuroprotective for making pharmacologic transformation immediate need. Herein, vasoactive intestinal peptide receptor-2 (VIPR2) agonist, LBT-3627, was developed as neuroprotectant PD-associated dopaminergic neurodegeneration. Employing both 6-hydroxydopamine (6-OHDA) α-synuclein...
Human immunodeficiency virus theranostics facilitates the development of long acting (LA) antiretroviral drugs (ARVs) by defining drug-particle cell depots. Optimal drug formulations are made possible based on precise particle composition, structure, shape and size. Through creation rod-shaped particles defined sizes reflective native LA drugs, theranostic probes can be deployed to measure particle-cell tissue biodistribution, activities retention. Methods: Herein, we created multimodal...
Alzheimer's disease (AD) is the most common neurodegenerative disorder. Pathologically, characterized by deposition of amyloid beta (Aβ) plaques and presence neurofibrillary tangles. These drive microglia neuroinflammation consequent neurodegeneration. While means to affect Aβ plaque accumulation pharmacologically was achieved, how it affects outcomes remains uncertain. Cerium oxide (CeO2) reduces plaques, oxidative stress, inflammation, AD signs symptoms. In particular, CeO2 nanoparticles...
The mixed lineage kinase type 3 inhibitor URMC-099 facilitates amyloid-beta (Aβ) clearance and degradation in cultured murine microglia. One putative mechanism is an effect of on Aβ uptake degradation. As promotes endolysosomal protein trafficking reduces microglial pro-inflammatory activities, we assessed whether these responses affect pathobiogenesis. To this end, URMC-099's therapeutic potential, precursor protein/presenilin-1 (APP/PS1) double-transgenic mice, was investigated model...
Abstract Background Dysregulation of innate and adaptive immunity heralds both the development progression Parkinson's disease (PD). Deficits in PD are defined by impairments monocyte activation, function, pro‐inflammatory secretory factors. Each influences pathobiology. Methods Results To define biomarkers associated with immune transformative therapy for PD, changes gene protein expression were evaluated before during treatment recombinant human granulocyte‐macrophage colony‐stimulating...
Abstract INTRODUCTION Transgenic mice overexpressing familial Alzheimer's disease (AD) mutations (FAD) show non‐physiological traits, and their immunocompetent backgrounds limit use in AD immunotherapy research. Preclinical models that reflect human immune responses are needed. METHODS Using CRISPR‐Cas9, we developed single (NA) double (NAPS) knock‐in (KI) amyloid precursor protein (APP) KM670,671NL (Swedish) presenilin 1 (PS 1) M146V FAD on an immunodeficient NOG (NOD.Cg‐Prkdc scid Il2rg...
Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective responses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric microsphere system was developed for chemically inactivated proteins. SARS-CoV-2 proteins encapsulated in microspheres induced robust immunity. The antigen-loaded can preclude the need repeat...