NeuroImmune pharmacology and therapeutics最新文献

Objectives: HIV suppression in brain viral reservoirs, especially macrophages, and microglia is critical to suppress HIV neuropathogenesis and subsequently HIV-associated neurocognitive disorders (HAND). Since most antiretroviral therapy (ART) drugs do not achieve optimal therapeutic concentrations in the brain and can cause neurotoxicity, an alternative/adjuvant therapy is needed to suppress HIV neuropathogenesis. In this study, our objectives were to examine the anti-HIV, antioxidant, and anti-inflammatory potential of resveratrol (RES) and its synthetic analogs 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) and 4-(E)-{(4-hydroxyphenylimino)-methylbenzene,1,2-diol} (HPIMBD) in HIV-infected macrophages.

Methods: We used HIV replication (viral load), oxidative stress (reactive oxygen species and antioxidant enzymes), and inflammatory response (pro- and anti-inflammatory cytokines/chemokines) assays to achieve the objectives of the study.

Results: Our results showed that RES and its analogs HPIMBD and TIMBD at 25 µM concentration significantly decrease HIV replication in both primary monocyte-derived macrophages and U1-differentiated macrophages. Moreover, RES and its analogs do not induce any cytotoxicity for up to 3 days in these cells. Further, treatment with RES and TIMBD (25 µM) also reduced the levels of reactive oxygen species without affecting the expression of antioxidant enzymes, SOD1, and catalase in U1 macrophages. Besides, RES and HPIMBD treatment inhibited the proinflammatory cytokines and chemokines in U1 macrophages, which was associated with decreased levels of anti-inflammatory cytokines. Importantly, our western blot experiments show that RES also decreases cellular proinflammatory cytokine IL-1β, which is usually elevated in both myeloid and neuronal cells upon HIV infection.

Conclusions: Taken together, our results suggest that RES and/or its analogs are important adjuvants that may be used not only to suppress HIV but also oxidative stress and inflammation in brain viral reservoirs.

Alzheimer's disease (AD) is the most common cause of dementia. While pathologic hallmarks, such as extracellular beta-amyloid plaques, are well-characterized in affected individuals, the pathogenesis that causes plaque formation and eventual cognitive decline is not well understood. A recent resurgence of the decades-old "infectious hypothesis" has garnered increased attention on the potential role that microbes may play in AD. In this theory, it is thought that pathogens such as viruses may act as seeds for beta-amyloid aggregation, ultimately leading to plaques. Interest in the infectious hypothesis has also spurred further investigation into additional characteristics of viral infection that may play a role in AD progression, such as neuroinflammation, latency, and viral DNA integration. While a flurry of research in this area has been recently published, with herpesviruses being of particular interest, the role of pathogens in AD remains controversial. In this review, the insights gained thus far into the possible role of herpesviruses in AD are summarized. The challenges and potential future directions of herpesvirus research in AD and dementia are also discussed.

Objective: To quantify neuropsychiatric symptoms reported by individuals with Post-Acute Sequelae of COVID-19 (PASC) using the NIH Toolbox^® for Assessment of Neurological and Behavioral Function (NIHTB) and Patient-Reported Outcomes Measurement Information System (PROMIS).

Methods: 30 PASC (20 women, 21-63 years) and 27 control (16 women, 25-68 years) participants completed three NIHTB batteries and selected PROMIS tests. Group differences on fully corrected T-scores were evaluated using analysis of covariance and Cohen's d effect sizes. A linear regression model predicted the effects from time since diagnosis.

Results: PASC had poorer emotional health and motor function than controls, including poorer locomotion, endurance and dexterity, but normal cognitive function, ~7 months post-infection, compared to controls. PASC participants had a steeper age-related decline on 2-Minute Walk than controls. T-scores on four cognitive and three motor tests improved with longer time since diagnosis.

Conclusion: NIHTB and PROMIS captured the poorer emotional health and motor function in PASC, including the novel findings of deficits locomotion and dexterity. The normal cognitive performance suggests subclinical effects that may be compensated by neural and cognitive reserves, and manifested subjectively by the negative psychological effects and fatigue. The persistent emotional and psychiatric symptoms necessitate mental health treatment be prioritized.

The 27th Scientific Conference of the Society on Neuroimmune Pharmacology (SNIP) in New Delhi, India, on March 15-18, 2023 is a historic summit of experts from around the world. The four day conference provides insights into the latest and most advanced science in the intersecting areas of neuroscience, immunology, pharmacology, and its translational aspects, in particular, HIV and drug abuse. Abstracts are ordered in three major groups: (1) Symposium speakers (S1-S64), (2) Investigator Posters (I1-I18), and (3) Trainee Poster (T1-T28).

Background: We recently reveal that anti-CD4 autoantibodies contribute to blunted CD4+ T cell reconstitution in HIV+ individuals on antiretroviral therapy (ART). Cocaine use is common among HIV+ individuals and is associated with accelerated disease progression. However, the mechanisms underlying cocaine-induced immune perturbations remain obscure.

Methods: We evaluated plasma levels of anti-CD4 IgG and markers of microbial translocation, as well as B-cell gene expression profiles and activation in HIV+ chronic cocaine users and non-users on suppressive ART, as well as uninfected controls. Plasma purified anti-CD4 IgGs were assessed for antibody-dependent cytotoxicity (ADCC).

Results: HIV+ cocaine users had increased plasma levels of anti-CD4 IgGs, lipopolysaccharide (LPS), and soluble CD14 (sCD14) versus non-users. An inverse correlation was observed in cocaine users, but not non-drug users. Anti-CD4 IgGs from HIV+ cocaine users mediated CD4+ T cell death through ADCC in vitro. B cells from HIV+ cocaine users exhibited activation signaling pathways and activation (cycling and TLR4 expression) related to microbial translocation versus non-users.

Conclusions: This study improves our understanding of cocaine associated B cell perturbations and immune failure and the new appreciation for autoreactive B cells as novel therapeutic targets.