Circadian disruption and psychostimulants dysregulates plasma acute-phase proteins and circulating cell-free mitochondrial DNA.

Background: Previous studies have indicated a close link between the inflammatory response, exacerbated by circadian disruption and psychostimulants such as cocaine and methamphetamine (METH). Indicators of this inflammation include cortisol and acute-phase proteins (APPs) like C-reactive protein (CRP), complement C3 (C3), and serum amyloid A (SAA). The connection between these inflammation markers and circulating mitochondrial DNA (mtDNA) has been gaining attention.

Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures.

Disturbances in the circadian rhythm alter the normal sleep-wake cycle, which increases vulnerability to drug abuse. Drug abuse can disrupt several homeostatic processes regulated by the circadian rhythm and influence addiction paradigms, including cravings for cocaine. The relationship between circadian rhythm and cocaine abuse is complex and bidirectional, and disruption impacts both brain function and metabolic profiles.

Epigenetic signature of N-terminal acetyltransferases: a probable mediator of immune and neuropathogenesis in HIV infection.

HIV is a major global public threat burdening society, yet the exact mechanism of HIV pathogenesis needs to be elucidated. In the era of epigenetic therapy, N-terminal acetylation (Nt-acetylation) changes induced by viral infection might play a critical role in virus-host interactions in HIV infection. The mitochondrial epigenetic mechanism, predominantly Nt acetylation, holds HIV immunopathogenesis and is vastly unexplored.

HIV-1 Tat and cocaine impact astrocytic energy reservoirs and epigenetic regulation by influencing the LINC01133-hsa-miR-4726-5p-NDUFA9 axis.

Clinical research has proven that HIV-positive (HIV) individuals with cocaine abuse show behavioral and neurocognitive disorders. Noncoding RNAs (ncRNAs), such as long ncRNAs (lncRNAs) and microRNAs (miRNAs), are known to regulate gene expression in the contexts of HIV infection and drug abuse. However, there are no specific lncRNA or miRNA biomarkers associated with HIV-1 Transactivator of transcription protein (Tat) and cocaine coexposure.

Psychostimulants influence oxidative stress and redox signatures: the role of DNA methylation.

Psychostimulant use induces oxidative stress and alters redox imbalance, influencing epigenetic signatures in the central nervous system (CNS). Among the various epigenetic changes, DNA methylation is directly linked to oxidative stress metabolism via critical redox intermediates such as NAD+, S-adenosylmethionine (SAM), and 2-oxoglutarate. Fluctuations in these intermediates directly influence epigenetic signatures, which leads to detectable alterations in gene expression and protein modification.

HIV-1 Tat and cocaine coexposure impacts piRNAs to affect astrocyte energy metabolism.

To understand the effect of HIV infection and cocaine exposure on piRNA expression in human primary astrocytes. We used small RNA sequencing analysis to investigate the impacts of HIV-1 Tat and cocaine coexposure on the expression of piRNAs in human primary astrocytes. We identified 27,700 piRNAs and analyzed them by small RNA next-generation sequencing.

Proteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes.

The chronic irreversible regression of cognitive ability and memory function in human immunodeficiency virus (HIV)-associated dementia (HAND) is linked with late-stage HIV infection in the brain. The molecular-level signatures of neuroinflammation and neurodegeneration are linked with dysfunction in HAND patients. Protein expression changes and posttranslational modification are epigenetic cues for dementia and neurodegenerative disease.

Influence of psychostimulants and opioids on epigenetic modification of class III histone deacetylase (HDAC)-sirtuins in glial cells.

Substance abuse affects the central nervous system (CNS) and remains a global health problem. Psychostimulants, such as cocaine and methamphetamine (METH), and opioids affect neuronal function and lead to behavioral impairments via epigenetic modification. Epigenetic changes occur via classical pathways, especially the class III histone deacetylase (HDAC)-sirtuin (SIRT) family, that act as cellular sensors to regulate energy homeostasis and coordinate cellular responses to maintain genome integrity.

HIV-1 Tat and cocaine impact astrocytic energy reservoir influence on miRNA epigenetic regulation.

Astrocytes are the primary regulator of energy metabolism in the central nervous system (CNS), and impairment of astrocyte's energy resource may trigger neurodegeneration. HIV infections and cocaine use are known to alter epigenetic modification, including miRNAs, which can target gene expression post-transcriptionally. However, miRNA-mediated astrocyte energy metabolism has not been delineated in HIV infection and cocaine abuse.

Psychostimulants and opioids differentially influence the epigenetic modification of histone acetyltransferase and histone deacetylase in astrocytes.

Illicit drugs are known to affect central nervous system (CNS). Majorly psychostimulants such as cocaine, methamphetamine (METH) and opioids such as morphine are known to induce epigenetic changes of histone modifications and chromatin remodeling which are mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). Aberrant changes in histone acetylation-deacetylation process further exacerbate dysregulation of gene expression and protein modification which has been linked with neuronal impairments including memory formation and synaptic plasticity.

HIV-1 Tat and cocaine impact mitochondrial epigenetics: effects on DNA methylation.

Human immunodeficiency virus (HIV) infection and the psychostimulant drug cocaine are known to induce epigenetic changes in DNA methylation that are linked with the severity of viral replication and disease progression, which impair neuronal functions. Increasing evidence suggests that changes in DNA methylation and hydroxymethylation occur in mitochondrial DNA (mtDNA) and represent mitochondrial genome epigenetic modifications (mitoepigenetic modifications). These modifications likely regulate both mtDNA replication and gene expression.

HIV-Tat and Cocaine Impact Brain Energy Metabolism: Redox Modification and Mitochondrial Biogenesis Influence NRF Transcription-Mediated Neurodegeneration.

HIV infection and drugs of abuse induce oxidative stress and redox imbalance, which cause neurodegeneration. The mechanisms by which HIV infection and cocaine consumption affect astrocyte energy metabolism, and how this leads to neurodegenerative dysfunction, remain poorly understood. Presently, we investigated how oxidative injury causes the depletion of energy resources and glutathione synthetase (GSS), which in turn activates 5' AMP-activated protein kinase (AMPK), glycolytic enzymes, and mitochondrial biogenesis, finally resulting in nuclear factor erythroid (NRF) transcription in astrocytes.

Neuroprotective Effect of Piracetam against Cocaine-Induced Neuro Epigenetic Modification of DNA Methylation in Astrocytes.

Cocaine abuse is known to alter mitochondrial biogenesis and induce epigenetic modification linked with neuronal dysfunction. Cocaine-induced epigenetic modification of DNA methylation and the mitochondrial genome may affect mitochondrial DNA (mtDNA) and nuclear DNA (nDNA), as epigenetic DNA methylation is key to maintaining genomic integrity in the central nervous system (CNS). However, the impact of cocaine-mediated epigenetic changes in astrocytes has not yet been elucidated.

Effects of Drugs of Abuse on the Blood-Brain Barrier: A Brief Overview.

The use of psychostimulants and alcohol disrupts blood-brain barrier (BBB) integrity, resulting in alterations to cellular function, and contributes to neurotoxicity. The BBB is the critical boundary of the central nervous system (CNS) where it maintains intracellular homeostasis and facilitates communication with the peripheral circulation. The BBB is regulated by tight junction (TJ) proteins that closely interact with endothelial cells (EC).

Oxidative Stress in HIV Infection and Alcohol Use: Role of Redox Signals in Modulation of Lipid Rafts and ATP-Binding Cassette Transporters.

Aims: Human immunodeficiency virus (HIV) infection induces oxidative stress and alcohol use accelerates disease progression, subsequently causing immune dysfunction. However, HIV and alcohol impact on lipid rafts-mediated immune dysfunction remains unknown. In this study, we investigate the modulation by which oxidative stress induces reactive oxygen species (ROS) affecting redox expression, lipid rafts caveiloin-1, ATP-binding cassette (ABC) transporters, and transcriptional sterol regulatory element-binding protein (SREBP) gene and protein modification and how these mechanisms are associated with arachidonic acid (AA) metabolites in HIV positive alcohol users, and how they escalate immune dysfunction.

Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection.

Although the introduction of antiretroviral therapy has reduced the prevalence of severe forms of neurocognitive disorders, human immunodeficiency virus (HIV)-1-associated neurocognitive disorders were observed in 50% of HIV-infected patients globally. The blood-brain barrier is known to be impermeable to most of antiretroviral drugs. Successful delivery of antiretroviral drugs into the brain may induce an inflammatory response, which may further induce neurotoxicity.

HIV and Cocaine Impact Glial Metabolism: Energy Sensor AMP-activated protein kinase Role in Mitochondrial Biogenesis and Epigenetic Remodeling.

HIV infection and cocaine use have been identified as risk factors for triggering neuronal dysfunction. In the central nervous system (CNS), energy resource and metabolic function are regulated by astroglia. Glia is the major reservoir of HIV infection and disease progression in CNS.

Effect of Cocaine on HIV Infection and Inflammasome Gene Expression Profile in HIV Infected Macrophages.

We have observed significantly increased HIV infection in HIV infected macrophages in the presence of cocaine that could be due to the downregulation of BST2 restriction factor in these cells. In human inflammasome PCR array, among different involved in inflammasome formation, in HIV infected macrophages in the presence of cocaine, we have observed significant upregulation of NLRP3, AIM2 genes and downstream genes IL-1β and PTGS2. Whereas negative regulatory gene MEFV was upregulated, CD40LG and PYDC1 were significantly downregulated.

Profile of Class I Histone Deacetylases (HDAC) by Human Dendritic Cells after Alcohol Consumption and In Vitro Alcohol Treatment and Their Implication in Oxidative Stress: Role of HDAC Inhibitors Trichostatin A and Mocetinostat.

Epigenetic mechanisms have been shown to play a role in alcohol use disorders (AUDs) and may prove to be valuable therapeutic targets. However, the involvement of histone deacetylases (HDACs) on alcohol-induced oxidative stress of human primary monocyte-derived dendritic cells (MDDCs) has not been elucidated. In the current study, we took a novel approach combining ex vivo, in vitro and in silico analyses to elucidate the mechanisms of alcohol-induced oxidative stress and role of HDACs in the periphery.

Natural Products as Anti-HIV Agents and Role in HIV-Associated Neurocognitive Disorders (HAND): A Brief Overview.

As the threat of Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) persists to rise, effective drug treatments are required to treat the infected people. Even though combination antiretroviral therapy (cART) provides stable viral suppression, it is not devoid of undesirable side effects, especially in persons undergoing long-term treatment. The present therapy finds its limitations in the emergence of multidrug resistance and accordingly finding new drugs and novel targets is the need of the hour to treat the infected persons and further to attack HIV reservoirs in the body like brain, lymph nodes to achieve the ultimate goal of complete eradication of HIV and AIDS.

Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC).

During human immunodeficiency virus (HIV) infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role. For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages. Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC).

Synaptic Plasticity and Neurological Disorders in Neurotropic Viral Infections.

Based on the type of cells or tissues they tend to harbor or attack, many of the viruses are characterized. But, in case of neurotropic viruses, it is not possible to classify them based on their tropism because many of them are not primarily neurotropic. While rabies and poliovirus are considered as strictly neurotropic, other neurotropic viruses involve nervous tissue only secondarily.

HIV-1 gp120 and morphine induced oxidative stress: role in cell cycle regulation.

HIV infection and illicit drugs are known to induce oxidative stress and linked with severity of viral replication, disease progression, impaired cell cycle regulation and neurodegeneration. Studies have shown that morphine accelerates HIV infection and disease progression mediated by Reactive oxygen species (ROS). Oxidative stress impact redox balance and ROS production affect cell cycle regulation.

Effect of human immunodeficiency virus on blood-brain barrier integrity and function: an update.

The blood-brain barrier (BBB) is a diffusion barrier that has an important role in maintaining a precisely regulated microenvironment protecting the neural tissue from infectious agents and toxins in the circulating system. Compromised BBB integrity plays a major role in the pathogenesis of retroviral associated neurological diseases. Human Immunodeficiency Virus (HIV) infection in the Central Nervous System (CNS) is an early event even before the serodiagnosis for HIV positivity or the initiation of antiretroviral therapy (ART), resulting in neurological complications in many of the infected patients.

HIV Subtypes B and C gp120 and Methamphetamine Interaction: Dopaminergic System Implicates Differential Neuronal Toxicity.

HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood.