A5072090047- HIV Research and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- HIV/AIDS Research and Interventions
- HIV-related health complications and treatments
- Mosquito-borne diseases and control
- HIV/AIDS drug development and treatment
- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Barrier Structure and Function Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Advanced Drug Delivery Systems
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Reproductive System and Pregnancy
- Plant Virus Research Studies
- Complement system in diseases
- Alzheimer's disease research and treatments
- Phagocytosis and Immune Regulation
- Eosinophilic Disorders and Syndromes
- Biochemical and Molecular Research
- COVID-19 Clinical Research Studies
- Nanoparticle-Based Drug Delivery
- RNA Interference and Gene Delivery
- Cancer-related molecular mechanisms research
- vaccines and immunoinformatics approaches
University of Nebraska Medical Center
2015-2024
University of Nebraska at Omaha
2013
Institute for Neurodegenerative Disorders
2007
University of Oklahoma Health Sciences Center
2001-2003
Texas Tech University
2002
Texas Tech University Health Sciences Center
2002
University of Cambridge
1998
University of Bristol
1993-1997
Human immunodeficiency virus-1 (HIV-1) encephalitis is characterized by brain infiltration of virus-infected monocytes and macrophages. Cellular products viral proteins secreted infected cells likely play an important role in blood–brain barrier (BBB) impairment the development HIV-1-associated dementia (HAD). We previously demonstrated that HIV-1 envelope glycoprotein gp120 induces toxicity alters expression tight junction human microvascular endothelial (HBMECs). Here, we delineate...
Abstract Potent antiretroviral activities and a barrier to viral resistance characterize the human immunodeficiency virus type one (HIV-1) integrase strand transfer inhibitor dolutegravir (DTG). Herein, long-acting parenteral DTG was created through chemical modification improve treatment outcomes. A hydrophobic lipophilic modified prodrug is encapsulated into poloxamer nanoformulations (NMDTG) characterized by size, shape, polydispersity, stability. Retained intracytoplasmic NMDTG particles...
Following global efforts to increase antiretroviral therapy (ART) access in Sub-Saharan Africa, ART coverage among HIV-infected Cameroonians increased from 0% 2003 22% 2014. However, the success of current HIV treatment programs depends not only on ART, but also retention care and good adherence. This is necessary achieve viral suppression, prevent virologic failure, reduce transmission HIV/AIDS-related deaths. Previous studies Cameroon showed poor adherence, interruption, loss follow-up...
Breakdown of the blood-brain barrier (BBB) is commonly seen in patients with HIV-associated dementia (HAD) despite lack productive infection brain endothelium. It likely that secreted viral products play a major role BBB damage and development HAD. The objective this study to determine effects gp120 proteins on endothelial cell permeability junctional protein expression. Our results showed treatment cultured human cells for 24 hours increased monolayer. Also, caused disruption downregulation...
Background: Factors limiting the efficacy of conventional antiretroviral therapy for HIV-1 infection include treatment adherence, pharmacokinetics and penetration into viral sanctuaries. These affect rate mutation drug resistance. In attempts to bypass such limitations, nanoparticles containing ritonavir, indinavir efavirenz (described as nanoART) were manufactured assess macrophage-based delivery. Methods: NanoART made by high-pressure homogenization crystalline with various surfactants....
The disease burden of human immunodeficiency virus (HIV)--acquired syndrome (AIDS) is highest in sub-Saharan Africa but there are few studies on the associated neurocognitive disorders this region. objectives study were to determine whether Western neuropsychological (NP) methods appropriate for use Cameroon, and evaluate cognitive function a sample HIV-infected adults.
Lack of adherence, inaccessibility to viral reservoirs, long-term drug toxicities, and treatment failures are limitations current antiretroviral therapy (ART). These lead increased loads, medicine resistance, immunocompromise, comorbid conditions. To this end, we developed long-acting nanoformulated ART (nanoART) through modifications existing atazanavir, ritonavir, efavirenz suspensions in order establish cell tissue depots achieve sustained responses. NanoART's abilities affect immune...
COVID-19 progression often involves severe lung injury, inflammation, coagulopathy, and leukocyte infiltration into pulmonary tissues. The pathogenesis of these complications is unknown. Because vascular endothelium neutrophils express angiotensin-converting enzyme-2 spike (S)-proteins, which are present in bodily fluids tissues SARS-CoV-2-infected patients, we investigated the effect S-proteins cell-cell communication on human microvascular endothelial cells expression P-selectin, markers...
Breakdown of the blood-brain barrier is commonly seen in patients with human immunodeficiency virus (HIV)-associated dementia, despite lack productive HIV-infection brain endothelium. Through this damaged barrier, HIV and HIV-infected monocytes/macrophages infiltrate further infect microglia macrophages. Neuronal cell death dysfunction are underlying cause HIV-associated but no neurons has been documented. It likely that secreted viral products play a major role damage neuronal death. The...
Abstract: Despite the successes of antiretroviral therapy (ART), HIV-associated neurocognitive disorders remain prevalent in infected people. This is due, part, to incomplete ART penetration across blood–brain barrier (BBB) and lymph nodes establishment viral sanctuaries within central nervous system. In efforts improve delivery, our laboratories developed a macrophage-carriage system for nanoformulated crystalline (nanoART) (atazanavir, ritonavir, indinavir, efavirenz). We demonstrate that...
Background: Macrophage-carried nanoformulated catalase ('nanozyme') attenuates neuroinflammation and protects nigrostriatal neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication. This is facilitated by effective enzyme transfer blood-borne macrophages to adjacent endothelial cells leading the decomposition of reactive oxygen species. Materials & methods: We examined intra- inter-cellular trafficking mechanisms nanozymes confocal microscopy. Improved neuronal survival...
Abstract Background Neurocognitive impairment is present in 50% of HIV-infected individuals and often associated with Alzheimer’s Disease (AD)-like brain pathologies, including increased amyloid-beta (Aβ) Tau hyperphosphorylation. Here, we aimed to determine whether HIV-1 infection causes AD-like pathologies an HIV/AIDS humanized mouse model, the CCR5 antagonist maraviroc alters HIV-induced pathologies. Methods NOD/scid–IL-2Rγ c null mice engrafted human blood leukocytes were infected HIV-1,...
The mechanisms underlying blood—brain barrier (BBB) dysfunction seen in human immunodeficiency virus 1 (HIV-1) infection are poorly understood; however, they believed to be caused by interactions of brain microvascular endothelial cells (HBMEC) with virus-infected macrophages. Using a transwell system and Affymetrix arrays, we investigated HIV-1-induced genomic changes HBMEC after coculture HIV-1-infected or -uninfected monocyte-derived macrophages (MDM). Differentially expressed genes were...
HIV-1 genetic differences influence viral replication and progression to AIDS. circulating recombinant form (CRF)02_AG is the predominant subtype infecting humans in West Central Africa, but its effects on HIV neuropathogenesis are not known. In present study, we investigated of Tat proteins from B (Tat.B) CRF02_AG (Tat.AG) primary human brain microvascular endothelial cells (HBMEC), major component blood–brain barrier (BBB). Using Affymetrix GeneChip Human Gene 1.0.ST arrays, showed that...