Microglia are the primary target and reservoir of HIV infection in the central nervous system (CNS), which contributes to HIV-associated neurocognitive disorder (HAND). However, studying HIV infection of microglia has been challenged by the limited availability of primary human microglial cells. To overcome this issue, investigators have developed various microglial models for HIV studies, including immortalized human microglial cell lines, HIV latently infected microglial clones, peripheral blood monocyte-derived microglia (MMG), induced pluripotent stem cell (iPSC)-derived microglia (iMg), and microglia-containing cerebral organoids (MCOs) from iPSCs. Though these models have been used in many laboratories, the published data about their expression of the specific human microglia markers and the HIV entry receptors are conflicting. In addition, there is limited information about their feasibility and applicability as a suitable model for acute and/or latent HIV infection. This review provides a concise summary of the currently used human microglial models, with a focus on their suitability for NeuroHIV research.

Microglia are the primary target and reservoir of HIV infection in the central nervous system (CNS) which contribute to HIV-associated neurocognitive disorder (HAND). However, studying HIV infection of microglia has been challenged by limited availability of primary human microglial cells. To overcome this issue, investigators have developed various microglial models for HIV studies, including immortalized human microglial cell lines, HIV latently infected microglial clone, peripheral blood monocyte-derived microglia (MMG), induced pluripotent stem cell (iPSC)-derived microglia (iMg) and microglia containing cerebral organoids (MCOs) from iPSC. Though these models have been used in many laboratories, the published data about their expression of the specific human microglia markers and the HIV entry receptors is conflicting. In addition, there is limited information about their feasibility and applicability as a suitable model for acute and/or latent HIV infection. This review provides a concise summary of the currently used human microglial models with a focus on their suitability for NeuroHIV research.

Diabetic patients are always at a higher risk of ischemic diseases like coronary artery diseases. One such ischemic carotid artery disease is Moyamoya. Moyamoya disease (MMD) has been associated with diabetes Type-I and II and the causality was unclear. RNF213 is the major susceptible gene for MMD. To understand the association between diabetes mellitus and MMD we chose the major players from both the anomalies, insulin and RNF213. But before establishing a role of RNF213 in insulin regulating pathway we had to understand the involvement of RNF213 within different biological systems. For this we have adopted a preliminary computational approach to understand the prominent interactions of RNF213. Our first objective was to construct an interactome for RNF213. We have analyzed several curated databases and adapted a list of RNF213 interacting partners to develop its interactome. Then to understand the involvement of this interactome in biological functions we have analyzed major biological pathways, biological processes and prominent clusters related to this interactome through computational approach. Then to develop a pathway that might give clue for RNF213 involvement in insulin regulatory pathway we have validated the intercluster and intracluster predictions and identified a regulatory pathway for RNF213. RNF213 interactome was observed to be involved in adaptive immunity with 4 major clusters; one of the cluster involved TNFα. Immune system involves several pathways, and therefore at this point we have chosen an event-based strategy to obtain an explicit target. Immunity is mediated by many pro-inflammatory cytokines like TNFα. TNFα-mediated inflammation, obesity and insulin resistance are associated. Therefore we chose to explore the role of RNF213 in TNFα-mediated inflammation in macrophages and inflammation-mediated insulin-resistance in adipocytes. We have observed an enhancement of RNF213 gene expression by LPS mediated pro-inflammatory stimuli and suppression by PPARγ-mediated anti-inflammatory, insulin sensitizing stimuli in macrophages. A more significant response was observed in adipocytes as well. Administration of the pro-inflammatory cytokine TNFα was able to impede the reduction in RNF213 expression during adipogenesis and this effect was observed to be mediated by PTP1B. Inactivation of PTP1B abolished RNF213 expression which in turn enhanced the adipogenesis process through enhanced PPARγ. Constitutive expression of RNF213 suppressed the adipocyte differentiation by the inhibition of PPARγ. We could show the expression of RNF213 has been regulated by TNFα/PTP1B pathway and PPARγ. The constitutive expression of RNF213 during adipogenesis appears to be an adipostatic measure that obese patients acquire to inhibit further adipogenesis. This is verified in silico by analyzing the gene expression data obtained from Gene Expression Omnibus database, which showed a higher expression of RNF213 in adipose tissue samples of obese people. Overall this study gives new insights in the TNFα-mediated pathway in adipogenesis and suggests a role of RNF213 in adipogenesis via this pathway.

Background: Plant derived compounds, naringenin and ellagic acid might interfere in MTT (3-(4, 5- Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide) assay in the form of reducing the tetrazolium salt in the absence of cells. Objective: Effect of naringenin and ellagic acid in MTT assay. Methods: MTT assay has been performed at different conditions like, varying the concentration of phytocompounds, incubation time, and changing the media. Results: Ellagic acid at the concentration of 80 μg/ml showed maximum absorbance of 0.579 in the presence of RPMI media (Roswell Park Memorial Institute Medium) that has 10% newborn calf serum. Naringenin showed higher absorbance of 2.74 at 80 μg/ml in RPMI media that has 10% newborn calf serum. Naringenin and Ellagic acid had better ability to reduce the MTT in the presence of RPMI media than anhydrous ethanol. Conclusion: Naringenin reduced the MTT better than ellagic acid in RPMI-1640 medium. These results show the need to be cautious of choosing MTT assay to measure the metabolic activity of cells treated with phytocompounds.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder that affects millions of people globally. Although the mechanisms of COPD pathogenesis are not completely known, oxidative stress and lung inflammation caused by chronic exposure to cigarette smoke, environmental or occupational pollutants, gas from burning biomass fuel are thought to contribute to development of COPD. Therefore, therapies aimed at reducing oxidative stress along with inflammation may be important in treating COPD. However, the current pharmacological therapies treat symptoms and reduce acute exacerbations, but do not treat the root cause of COPD. Quercetin is a plant polyphenol present in berries, apples and onions, and has potent antioxidant and anti-inflammatory properties. Quercetin inhibits oxidative stress by scavenging reactive oxidant species and promoting expression of antioxidant enzymes. It reduces inflammation by inhibiting various kinases that participate in the expression of pro-inflammatory cytokines. It also alters gene expression by functioning as an epigenetic modifier. Quercetin also acts as antiviral agent by attenuating viral entry and replication. In preclinical models of COPD, quercetin reduces oxidative stress, lung inflammation, goblet cell metaplasia, expression of matrix metalloprotease MMP-9 and MMP-12, and prevents rhinovirus-induced progression of emphysema. It also promotes normal regeneration of airway epithelium by improving cell polarization, reducing goblet cell hyperplasia and increasing number of ciliated cells. This review compiles the current understanding of the biological properties of quercetin and its potential therapeutic role in COPD. We also summarize its potential benefits over the current therapeutic drugs used to treat COPD.