Volume 4, Issue 4

Objective HIV-1 infection affects approximately 38.4 million people around the world. The advent of combination anti-retroviral therapy (cART) has greatly improved the quality of life of infected individuals; however, roughly 50 % of these individuals will still experience HIV-1-associated neurocognitive disorders (HAND). Additionally, the gastrointestinal microbiome has been reported to be dysbiotic in HIV-1 infected individuals, regardless of adherence to cART. Current research has pointed to the gut-brain-microbiota axis as a potential target to treat both cognitive deficits and microbial changes. The present study investigated S-Equol (SE) as a potential therapeutic for HAND by modulating the gastrointestinal microbiome. Methods The study included 21 HIV-1 Tg rats and 21 F344 control animals to test the effect 0.2 mg SE has on cocaine-maintained responding on a PR schedule of reinforcement. Results Gastrointestinal microbiome alterations between genotypes were found at the phylum and genus level, regardless of treatment group, and SE treatment had both main effects and interactions with genotype. Prevotella_UCG_001 was significantly associated with lever presses for drug, suggesting an effect on motivation for cocaine. Alloprevotella was found to significantly differentiate between genotype by treatment effects, indicating that SE differently affects genotypes. Conclusions SE may provide a novel adjuvant treatment in addition to cART for HIV-1-associated dysbiosis and associated neurocognitive dysfunction.

Objectives We aimed to cross-sectionally and longitudinally compare brain morphometry and neuropsychiatric symptoms, and evaluate their relationship, in participants with Post-Coronavirus Disease Condition (PCC) and healthy Controls. Methods At Baseline, 29 PCC (19 female; average age = 42.4 ± 12.2 years; 242 ± 156 days since infection) and 25 Controls (14 female; 44.1 ± 12.3 years) completed the NIH Toolbox Emotion, Motor and Cognition Batteries; Patient Reported Outcomes Measurement Information System (PROMIS); and structural brain MRI (thickness, areas, volumes). We compared neurobehavioral performance on the NIH Toolbox and PROMIS and structural brain morphometry for 34 cortical regions and 8 subcortical volumes, between PCC and matched Controls at Baseline (∼8 months post-infection) and 11 PCC and 7 Controls at a Follow-Up visit (∼3 years post-infection). Results At Baseline, PCC had significantly larger putamen and amygdala (FDR-corrected p = 0.04; +5.3 and 5.9 %) and a trend for larger hippocampus and accumbens (uncorrected-p = 0.012 and 0.027, +5.1 and 12.9 %) than Controls. PCC also tended to have 4 thicker cortices (p = 0.010–0.049; +3.6–6.5 %), 6 larger surface areas (p = 0.009–0.023; +5.9–8.6 %), and 9 larger cortical volumes (p = 0.003–0.008; +4.2–10.7 %). These abnormal measures were associated with more anxiety, depression, and pain ( r = 0.5–0.75; p = 0.005–0.04). At Follow-Up, PCC had more sadness, fear, pain, and fatigue compared to Controls. However, group differences in morphometry diminished and PCC neurobehavioral performance tended to improve. Conclusions Structural abnormalities in PCC suggest compensatory processes such as enhanced myelination or neurogenesis, rather than neuroinflammation, which in turn may contribute to persistent neurobehavioral symptoms. However, these alterations and symptoms may improve three years after infection.

Objectives Opioid use during pregnancy is associated with adverse perinatal outcomes, but its effects on placental biology are not well understood. Because the placenta plays a vital role in fetal development and immune regulation, we examined how maternal opioid exposure influences microbial DNA signatures and immune gene expression in the placenta. Methods Placentas from opioid-exposed and control C57 BL/6 female mice were analyzed through 16S rRNA gene sequencing, bulk RNA sequencing and pathway enrichment analysis. Results Opioid-exposed placentas showed altered microbial DNA profiles, including increased α-diversity and enrichment of Staphylococcus spp. Transcriptomic analysis revealed 357 differentially expressed genes, emphasizing immune pathways, including dendritic cell-NK cell crosstalk, immunogenic cell death, and cytokine storm signaling. STAT3 signaling and heparan sulfate biosynthesis were downregulated. Pathways related to apoptosis, cytotoxicity, and neonatal death were upregulated. Conclusions Maternal opioid exposure may disrupt placental microbial and immune environments, potentially leading to structural compromise through immune-mediated cellular apoptosis.

Currently, no US Food and Drug Administration-approved treatments exist to manage HIV-associated sensory neuropathy (HIV-SN) and management is largely confined to adjusting antiretroviral therapy (ART) doses and medications. Thus, this urgent health crisis requires strong research commitment to identify a cure or palliative treatment. This review explores the current state-of-the-art related to HIV-SN. It first explores recent developments in the understanding of HIV-SN, emphasizing the importance of developments in the HIV-SN mouse model and non-myelination intra epidermal never fiber denervation. Next, the neurotoxic side effects of ART are summarized. Finally, we explore the interactions and synergy between HIV-SN and ART in the pathogenesis of peripheral neuropathy. While the overall mortality related to HIV has decreased significantly in recent decades, further elucidation of the exact mechanisms of HIV-SN is needed to better treat patients living with HIV as a chronic condition.

Extracellular vesicles (EVs) are mediators of neurodegeneration and emerging therapeutic tools for central nervous system disorders. On the one hand, they help spread beta amyloid, tau, α -synuclein, TDP-43, and mutant SOD1, contributing to the signs and symptoms of Alzheimer’s, Parkinson’s, Amyotrophic lateral sclerosis, and Huntington’s Diseases. By activating glial cells, they promote chronic neuroinflammation through carrying cytokines, inflammasomes, and chemokines. On the other hand, EVs’ ability to transport neuroregulatory products and cross the blood–brain barrier makes them ideal vehicles for drug delivery. Their function can be surface-modified to deliver targeted therapies, including anti-inflammatory and neuroprotective regulatory RNAs, proteins, and lipids, as well as factors that help maintain neural homeostasis. Notably, we suggest that colostrum-derived EVs, enriched with growth factors and immune-regulatory microRNAs, offer a natural, scalable, and biocompatible source for neuroprotective treatment. Although EVs can act as “Janus-faced” entities – serving both as disease initiators and versatile therapeutic vehicles – controlling their activity can enable immune-based therapeutics for neurodegenerative diseases.