Short-term exposure to JUUL electronic cigarettes can worsen ischemic stroke outcome.

Background: The short and long-term health effects of JUUL electronic cigarette (e-Cig) are largely unknown and warrant extensive research. We hypothesized that JUUL exposure could cause cerebrovascular toxicities impacting the progression and outcome of ischemic stroke comparable to tobacco smoke (TS) exposure.

Methods: We exposed male C57 mice to TS/JUUL vapor for 14 days.

Glutamate Buffering Capacity and Blood-Brain Barrier Protection of Opioid Receptor Agonists Biphalin and Nociceptin.

Opioids play crucial roles in the regulation of many important brain functions including pain, memory, and neurogenesis. Activation of opioid receptors is reported to have neuroprotective effects after ischemic reperfusion injury. The objective of this study was to understand the role of biphalin and nociceptin, opioid receptor agonists, on blood-brain barrier (BBB) integrity during ischemic stroke.

Repurposing metformin to treat age-related neurodegenerative disorders and ischemic stroke.

Aging is a risk factor for major central nervous system (CNS) disorders. More specifically, aging can be inked to neurodegenerative diseases (NDs) because of its deteriorating impact on neurovascular unit (NVU). Metformin, a first line FDA-approved anti-diabetic drug, has gained increasing interest among researchers for its role in improving aging-related neurodegenerative disorders.

Nano-synergistic combination of Erlotinib and Quinacrine for non-small cell lung cancer (NSCLC) therapeutics - Evaluation in biologically relevant in-vitro models.

Non-small cell lung cancer (NSCLC), pre-dominant subtype of lung cancer, is a global disorder affecting millions worldwide. One of the early treatments for NSCLC was use of a first-generation tyrosine kinase inhibitor, Erlotinib (Erlo). However, chronic exposure to Erlo led to development of acquired drug resistance (ADR) in NSCLC, limiting the clinical use of Erlo.

The Role of Smoking and Nicotine in the Transmission and Pathogenesis of COVID-19.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 virus, is turning out to be one of the most devastating global pandemics in the history of humankind. There is a shortage of effective therapeutic strategies or preventative vaccines for this disease to date. A rigorous investigation is needed for identifying and developing more effective therapeutic strategies for COVID-19.

Repurposing Quinacrine for Treatment of Malignant Mesothelioma: In-Vitro Therapeutic and Mechanistic Evaluation.

Malignant mesothelioma (MM) is a rare type of cancer primarily affecting mesothelial cells lining the pleural cavity. In this study, we propose to repurpose quinacrine (QA), a widely approved anti-malarial drug, for Malignant Pleural Mesothelioma (MPM) treatment. QA demonstrates high degree of cytotoxicity against both immortalized and primary patient-derived cell lines with sub-micromolar 50% inhibitory concentration (IC) values ranging from 1.

Exosomes in Ischemic Stroke.

Ischemic stroke, a leading cause of mortality, results in severe neurological outcomes in the patients. Effective stroke therapies may significantly decrease the extent of injury. For this purpose, novel and efficient drug delivery strategies need to be developed.

Novel approaches for the delivery of therapeutics in ischemic stroke.

Here, we review novel approaches to deliver neuroprotective drugs to salvageable penumbral brain areas of stroke injury with the goals of offsetting ischemic brain injury and enhancing recovery.

Development of inhalable quinacrine loaded bovine serum albumin modified cationic nanoparticles: Repurposing quinacrine for lung cancer therapeutics.

Drug repurposing is on the rise as an atypical strategy for discovery of new molecules, involving use of pre-existing molecules for a different therapeutic application than the approved indication. Using this strategy, the current study aims to leverage effects of quinacrine (QA), a well-known anti-malarial drug, for treatment of non-small cell lung cancer (NSCLC). For respiratory diseases, designing a QA loaded inhalable delivery system has multiple advantages over invasive delivery.

Prenatal electronic cigarette exposure decreases brain glucose utilization and worsens outcome in offspring hypoxic-ischemic brain injury.

It has been shown that prenatal nicotine and tobacco smoke exposure can cause different neurobehavioral disorders in the offspring. We hypothesize that prenatal exposure to nicotine-containing electronic cigarette (e-Cig) vapor can predispose newborn to enhanced sensitivity to hypoxic-ischemic (HI) brain injury and impaired motor and cognitive functions. In this study, pregnant CD1 mice were exposed to e-Cig vapor (2.

Brain Delivery of a Potent Opioid Receptor Agonist, Biphalin during Ischemic Stroke: Role of Organic Anion Transporting Polypeptide (OATP).

Transporters (expressed) at the blood-brain barrier (BBB) can play an essential role in the treatment of brain injury by transporting neuroprotective substance to the central nervous system. The goal of this study was to understand the role of organic anion transporting polypeptide (OATP1; OATP1A2 in humans and oatp1a4 in rodents) in the transport of a potent opioid receptor agonist, biphalin, across the BBB during ischemic stroke. Brain microvascular endothelial cells (BMECs) that were differentiated from human induced pluripotent stem cells (iPSCs) were used in the present study.

Cyclodextrin modified erlotinib loaded PLGA nanoparticles for improved therapeutic efficacy against non-small cell lung cancer.

This study was aimed at developing a nanoparticle strategy to overcome acquired resistance against erlotinib in non-small cell lung cancer (NSCLC). To load erlotinib on biodegradable PLGA nanoparticles, erlotinib-cyclodextrin (Erlo-CD) complex was prepared using β-cyclodextrin sulfobutyl ether, which was in turn loaded in the core of PLGA nanoparticles using multiple emulsion solvent evaporation. Nanoparticles were characterized for size distribution, entrapment and loading efficiency, in-vitro release, and therapeutic efficacy against different lung cancer cells.

Nintedanib-cyclodextrin complex to improve bio-activity and intestinal permeability.

Cyclodextrin complex of nintedanib was prepared aiming for increased bio-activity and improved transport across intestinal membrane with reduced p-glycoprotein (p-gp) efflux. Based on preliminary phase solubility studies and molecular modeling, sulfobutyl ether derivative of β-cyclodextrin (SBE-β-CD, Captisol) was selected to prepare inclusion complex. Complexation was confirmed using FTIR, 1H NMR, DSC, and XRD.

Neurovascular unit transport responses to ischemia and common coexisting conditions: smoking and diabetes.

Transporters at the neurovascular unit (NVU) are vital for the regulation of normal brain physiology via ion, water, and nutrients movement. In ischemic stroke, the reduction of cerebral blood flow causes several complex pathophysiological changes in the brain, one of which includes alterations of the NVU transporters, which can exacerbate stroke outcome by increased brain edema (by altering ion, water, and glutamate transporters), altered energy metabolism (by altering glucose transporters), and enhanced drug toxicity (by altering efflux transporters). Smoking and diabetes are common risk factors as well as coexisting conditions in ischemic stroke that are also reported to change the expression and function of NVU transporters.

Potential role of myo-inositol to improve ischemic stroke outcome in diabetic mouse.

Brain edema is one of the critical factors causing hightened disability and mortality in stroke patients, which is exaggerated further in diabetic patients. Organic osmolytes could play a critical role in the maintenance of cytotoxic edema. The present study was aimed to assess the role of myo-inositol, an organic osmolyte, on stroke outcome in diabetic and non-diabetic animals.

Nicotine and electronic cigarette (E-Cig) exposure decreases brain glucose utilization in ischemic stroke.

Previous studies in our laboratory have shown that nicotine exposure decreases glucose transport across the blood-brain barrier in ischemia-reperfusion conditions. We hypothesize that nicotine can also dysregulate brain parenchymal glucose utilization by altering glucose transporters with effects on sensitivity to ischemic stroke. In this study, we investigated the effects of nicotine exposure on neuronal glucose utilization using an in vitro ischemic stroke model.

The neuroprotective role of the brain opioid system in stroke injury.

Novel neuroprotective therapies are desperately needed to improve neuronal recovery after ischemic stroke and extend the therapeutic window or offset some of the adverse effects of tissue-type plasminogen activator (tPA). These advances could provide a more effective and safe therapeutic regimen for patients with ischemic stroke. The opioid system has gained intense interest over the past few years and is currently being investigated as a viable target for the pharmacological treatment of stroke.

Liposomes for the delivery of streptokinase.

Streptokinase is an efficient thrombolytic agent used to treat thromboembolic disorders. Conventional streptokinase formulations have limited thrombolytic activity and several shortcomings because of their immunogenicity and dose-related side effects including short half-life, lack of tissue targeting and peripheral bleeding. Different liposomal formulations have been explored by researchers in order to improve thrombolytic activity of streptokinase.

Zinc oxide nanoparticles: a promising nanomaterial for biomedical applications.

Zinc oxide (ZnO) nanoparticles (NPs) are a promising platform for use in biomedical research, especially given their anticancer and antimicrobial activities. These activities are associated with the ability of ZnO NPs to generate reactive oxygen species (ROS) and induce apoptosis. In addition, ZnO NPs have been successfully exploited as drug carriers for loading and transporting drugs to target sites, thereby reducing unwanted toxicity and off-target effects, and resulting in amplified synergistic effects.

Exploitation of Novel Molecular Targets to Treat Idiopathic Pulmonary Fibrosis: A Drug Discovery Perspective.

Background: Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing lung disease and is caused by excessive lung scarring. IPF-associated severe mortality can be attributed to late diagnosis due to its generic symptoms, and more importantly due to the lack of effective therapies available. Despite extensive research in the past decades, lung transplant still remains the most effective treatment for IPF.

Blood-Brain Barrier Protection as a Therapeutic Strategy for Acute Ischemic Stroke.

The blood-brain barrier (BBB) is a vital component of the neurovascular unit (NVU) containing tight junctional (TJ) proteins and different ion and nutrient transporters which maintain normal brain physiology. BBB disruption is a major pathological hallmark in the course of ischemic stroke which is regulated by the actions of different factors working at different stages of cerebral ischemia including matrix metalloproteinases (MMPs), inflammatory modulators, vesicular trafficking, oxidative pathways, and junctional-cytoskeletal interactions. These components interact further to disrupt maintenance of both the paracellular and transport barriers of the central nervous system (CNS) to worsen ischemic brain injury and the propensity for hemorrhagic transformation (HT) associated with injury and/or thrombolytic therapy with tissue-type plasminogen activator (tPA).

Advances in treatment of pulmonary arterial hypertension: patent review.

Current therapeutic approaches for pulmonary arterial hypertension (PAH) commonly include use of prostacyclins, endothelin pathway antagonists or NO (nitric oxide) pathway modulators. These agents are non-specific and suffer from several important shortcomings including short half-lives, invasive routes of administration, higher dose and frequency requirements, and several dose-related systemic side effects. Hence, discovery of novel agents with improved therapeutic efficacy with respect to survival benefits and the development of non-invasive routes of administration are in critical need.

Microfluidics-based 3D cell culture models: Utility in novel drug discovery and delivery research.

The implementation of microfluidic devices within life sciences has furthered the possibilities of both academic and industrial applications such as rapid genome sequencing, predictive drug studies, and single cell manipulation. In contrast to the preferred two-dimensional cell-based screening, three-dimensional (3D) systems have more in vivo relevance as well as ability to perform as a predictive tool for the success or failure of a drug screening campaign. 3D cell culture has shown an adaptive response to the recent advancements in microfluidic technologies which has allowed better control over spheroid sizes and subsequent drug screening studies.

Exosomes: Natural Carriers for siRNA Delivery.

Various cells of the human physiological system have the capability to release extracellular vesicles (EVs) involved in intercellular transport of proteins and nucleic acids. Exosomes are a subtype of extracellular vesicles having their origin through endocytic pathway. While being involved in intercellular transport of macromolecules, exosomes, due to their presence in several body fluids, can also be utilized as a system to commute RNA molecules and proteins in the body.