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eCD4-immunoglobulin (Ig) is an HIV entry inhibitor that mimics the engagement of both CD4 and CCR5 with the HIV envelope (Env) protein, a property that imbues it with remarkable potency and breadth. However, env is exceptionally genetically malleable and can evolve to escape a wide variety of entry inhibitors. Here we document the evolution of partial eCD4-Ig resistance in SHIV-AD8 EO -infected rhesus macaques (RMs) treated with adeno-associated virus vectors encoding eCD4-Ig. In one RM, setpoint viremia plateaued at 1,000 vRNA copies/mL, despite concomitant serum concentrations of eCD4-Ig in the 60-110 μg/mL range, implying that the virus had gained partial eCD4-Ig resistance. Env mutations occurring prominently in this animal were cloned and further characterized. Three of these mutations (R315G, A436T, and G471E) were sufficient to confer substantial resistance to eCD4-Ig-mediated neutralization onto the parental Env, accompanied by a marked loss of viral fitness. This resistance was not driven by decreased CD4 affinity, subverted sulfopeptide mimicry, changes to co-receptor tropism, or by a gain of CD4 independence. Rather, our data argue that the Env evolving in this animal attained eCD4-Ig resistance by decreasing triggerability, stabilizing the triggered state, and changing the nature of its relationship to the host CD4., Competing Interests: Declaration of interests M.A.M., M.D.A., M.R.G., and M.F. have significant financial interests in Emmune, Inc., a company that is developing HIV immunotherapies based on the immunoadhesin eCD4-Ig, and each serve in a consulting capacity for the company. These potential conflicts of interest are being managed by the authors’ respective institutions. None of the other authors or their immediate family members have any conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The chronic inflammatory condition known as multiple sclerosis (MS) causes inflammation and demyelination in the central nervous system (CNS). The activation of multiple cell types, including the CNS's resident immune cells called microglia, is a component of the immunological response in MS. Recently, the triggering receptor expressed on myeloid cells (TREM) family has emerged as a crucial player in modulating microglial function and subsequent neuroinflammation. Understanding the role of TREM receptors in MS pathogenesis could provide insightful information on how to develop new therapeutic approaches., Main Body: The TREM family consists of several receptors, including TREM-1 and TREM-2, which can be expressed on both immune cells, such as myeloid cells and microglia, and non-immune cells. These receptors interact with their respective ligands and regulate signaling pathways, ultimately leading to the control of microglial activation and inflammatory reactions. TREM-2, in particular, has garnered significant interest because of its connection with MS and other neurodegenerative diseases. The activation of microglia through TREM receptors in MS is thought to influence the equilibrium between helpful and detrimental inflammatory responses. TREM receptors can promote the phagocytosis of myelin debris and remove apoptotic cells, thus contributing to tissue repair and regeneration. However, excessive or dysregulated activation of microglia mediated by TREM receptors can lead to the release of pro-inflammatory cytokines and neurotoxic factors, exacerbating neuroinflammation and neurodegeneration in MS., Conclusion: The emerging role of the TREM family in demyelinating diseases highlights the importance of microglia in disease pathogenesis. Understanding the mechanisms by which TREM receptors modulate microglial function can provide valuable insights into the development of targeted therapies for these disorders. By selectively targeting TREM receptors, it may be possible to harness their beneficial effects on tissue repair while dampening their detrimental pro-inflammatory responses. Further research is warranted to elucidate the precise signaling pathways and ligand interactions involved in TREM-mediated microglial activation, which could uncover novel therapeutic avenues for treating MS and other neuroinflammatory disorders., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) poses significant challenges to regenerative medicine due to its limited self-repair capabilities. In this study, we engineered a biomimetic injectable hydrogel using modified chitosan and alginate biopolymers encapsulating selenium-folic acid nanoparticles (Se-FA NPs) to facilitate SCI regeneration. The hydrogel exhibited a unique porous structure attributed to the incorporation of nanofiber fragments, enhancing its biocompatibility and bioactivity. Through a series of in vitro evaluations, including cell viability assays, proliferation studies, gene expression analysis, we assessed the hydrogel's cytocompatibility and its potential for supporting neural cell growth. Our results demonstrate the promising efficacy of the hydrogel in providing a conducive microenvironment for neural tissue regeneration. Moreover, the sustained release of Se-FA NPs from the hydrogel system offers neuroprotective, antioxidative, and anti-inflammatory benefits crucial for SCI therapy. Overall, our biomimetic hydrogel biocomposites hold great potential as a therapeutic strategy for promoting spinal cord regeneration, highlighting their significance in advancing the field of regenerative medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Fampridine is the only drug approved by the US Food and Drug Administration (FDA) for people with multiple sclerosis (MS) to improve their movement and has exhibited a clinically significant improvement in gait function in a subset of MS patients with Expanded Disability Status Scale (ESDSS) from 4 to 7. Nevertheless, this drug has been reported to possess some adverse effects (AEs) like seizure because of its pharmacological features. The aim of this study was to evaluate the incidence rate of post-medication side effects (SEs) of fampridine in MS patients., Methods: This prospective cohort study includes MS patients aged between 18 and 65 years, referred to the neurology clinic of Kashani Hospital from April 2022 to October 2022, all with administration of fampridine (10 mg tablet twice daily according to the product specifications). Safety in these patients was monitored through monthly SEs checklist questions during 6 months of screening. SPSS version 18 was used to analyze the data of this study., Results: From 319 participants screened at baseline, 254 patients with MS, including 127 relapsing-remitting multiple sclerosis (RRMS), 101 secondary progressive multiple sclerosis (SPMS), and 26 primary progressive multiple sclerosis (PPMS), were included in the study. The most observed AEs in SPMS and RRMS patients were dry mouth (13.9% vs. 15%) and insomnia (12.9% vs. 11%), respectively. Urinary tract infection (UTI) (11.5%) and stomachache (11.5%) were the most common SEs in PPMS patients. The most severe complication of the patients was back pain, while digestive complications were less severe. Also, insomnia and UTI were the patients' most persistent SEs., Conclusions: The drug seems to be safe and well tolerated, as the SEs were mild and transient and they were consistent with most of the previous studies focusing on this medication., Competing Interests: There are no conflicts of interest., (Copyright: © 2025 International Journal of Preventive Medicine.)