Interactive effects of cocaine on HIV infection: implication in HIV-associated neurocognitive disorder and neuroAIDS.

Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV), but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine (DA) in the brain, by blocking the dopamine transporters (DAT) which is critical for DA homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to DA, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs), which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND). HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the blood brain barrier (BBB) in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies against HIV-1 infection in cocaine using HIV infected population

Oral administration of bovine milk-derived extracellular vesicles induces senescence in the primary tumor but accelerates cancer metastasis

The concept that extracellular vesicles (EVs) from the diet can be absorbed by the intestinal tract of the consuming organism, be bioavailable in various organs, and in-turn exert phenotypic changes is highly debatable. Here, we isolate EVs from both raw and commercial bovine milk and characterize them by electron microscopy, nanoparticle tracking analysis, western blotting, quantitative proteomics and small RNA sequencing analysis. Orally administered bovine milk-derived EVs survive the harsh degrading conditions of the gut, in mice, and is subsequently detected in multiple organs. Milk-derived EVs orally administered to mice implanted with colorectal and breast cancer cells reduce the primary tumor burden. Intriguingly, despite the reduction in primary tumor growth, milk-derived EVs accelerate metastasis in breast and pancreatic cancer mouse models. Proteomic and biochemical analysis reveal the induction of senescence and epithelial-to-mesenchymal transition in cancer cells upon treatment with milk-derived EVs. Timing of EV administration is critical as oral administration after resection of the primary tumor reverses the pro-metastatic effects of milk-derived EVs in breast cancer models. Taken together, our study provides context-based and opposing roles of milk-derived EVs as metastasis inducers and suppressors

Japanese encephalitis virus: an emerging pathogen

Japanese Encephalitis Virus (JEV) is a flavivirus maintained in a zoonotic cycle which involves pigs, birds and Culex species of mosquitoes causing fatal encephalitis endemic most of Asia and as far as Australia from its putative origin in Indonesia and Malaysia. The principle vector is Culex mosquito, most important being Culex tritaenorhynchus, present in greatest density in rainy season (June to November) Humans are accidental dead-end-hosts as they do not develop a level of viraemia sufficient to infect mosquitoes. The natural cycle of JEV consists of pig-mosquito-pig or bird-mosquito-bird and pigs serve as a biological amplifiers and reservoirs. The risk for Japanese encephalitis varies by appropriate ecological conditions and season to cause epidemics and epizootics. Disease control by vaccination is considered to be most effective. The Envelope (E) protein is dominant antigen including immunologic responses in infected host and eliciting virus neutralizing antibodies. Large scale immunization of susceptible human population is highly important to prevent this deadly infection. Attempts are being made to develop enhanced vaccines using the recombinant DNA technology. Since the existing inactivated, live attenuated or killed vaccines have side effects such as neurological disorders and systemic hypersensitivity, DNA based vaccines might aid the purpose of combating against JEV which are presently under clinical trials. Protection at personal level would help to reduce the incidence of the disease. In India vaccination against Japanese encephalitis are administered in areas where the disease is hyper-endemic.