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Introduction: Dimethyl sulfoxide (DMSO) is widely used as a diluent and/or solvent for pharmacological compounds. Furthermore, DMSO crosses the blood-brain barrier acting on the nervous system. The natural compounds phenylamides and lignanamides (LnHS) have protective effects on neuronal health, being promising neuroprotective candidates. In this scenario, we evaluated the impact of DMSO and/or LnHS on SH-SY5Y and U-87 cells, taken as in vitro model of neurons and glia. Methods: Cells were treated with DMSO and/or LnHS at different doses and proliferation (MTT and trypan blue counting, colony forming ability, autophagy, oxidative stress (NO, ROS determination) and inflammatory (IL8, IL6, TNFα mRNA expression) response was evaluated. Results: We found that DMSO reduces both neuronal and glial cell viability, while LnHS does not affect viability of SH-SY5Y cells but reduces that of U-87 cells. Therefore, we focused on SHSY5Y cells and investigated whether LnHS could counteract DMSO toxicity. LnHS partially attenuates the inhibitory effects of DMSO on cell viability and restores the colony-forming ability of SH-SY5Y cells exposed to DMSO. Furthermore, we found that co-administration of LnHS modulates the expression of SIRT3 and SOD2 enzymes, reduces nitrite release and ROS generation increasing IL-8 levels. Interestingly, co-administration of LnHS counteracts the DMSO-induced production of IL-6, while no modification in TNF-α was found. Discussion: Our study indicates LnHS as a potential feasible compound to support neuronal health as it counteracts DMSO induced cytotoxic effects by improving SH-SY5Y cells survival. Further studies are needed to clarify the molecular mechanisms underlying the LnHS biological activities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mallardo, Pacifico, Piccolella, Di Meo, Rizzo, Daniele and Nigro.)

Lyme disease is the most commonly reported vector-borne disease in the United States and is transmitted by Ixodes scapularis in the eastern US and I. pacificus in the west. The causative agents, Borrelia burgdorferi sensu stricto (Bbss) and B. mayonii belong to the B. burgdorferi sensu lato (Bbsl) species complex. An additional eight species of Bbsl have been identified in Ixodes species ticks in the US, but their geographic distribution, vector associations, human encounter rates and pathogenicity in humans are poorly defined. To better understand the geographic distribution and vector associations of Bbsl spirochetes in frequent and infrequent human-biting Ixodes species ticks in the US, we previously screened 29,517 host-seeking I. scapularis or I. pacificus ticks and 692 ticks belonging to eight other Ixodes species for Borrelia spirochetes using a previously described tick testing algorithm that utilizes a combination of real-time PCR and Sanger sequencing for Borrelia species identification. The assay was designed to detect known human pathogens spread by Ixodes species ticks, but it was not optimized to detect Bbsl co-infections. To determine if such co-infections were overlooked particularly in ticks infected with Bbss, we retested and analyzed a subsample of 845 Borrelia infected ticks using a next generation sequencing multiplex PCR amplicon sequencing (MPAS) assay that can identify Borrelia species and Bbsl co-infections. The assay also includes targets that can molecularly confirm identifications of Ixodes species ticks to better inform pathogen-vector associations. We show that Bbss is the most prevalent species in I. scapularis and I. pacificus; other Bbsl species were rarely detected in I. scapularis and the only Bbsl co-infections identified in I. scapularis were with Bbss and B. mayonii. We detected B. andersonii in I. dentatus in the Mid-Atlantic and Upper Midwest regions, B. kurtenbachii in I. scapularis in the Upper Midwest, B. bissettiae in I. pacificus and I. spinipalpis in the Northwest, and B. carolinensis in I. affinis in the Mid-Atlantic and Southeast, and B. lanei in I. spinipalpis in the Northwest. Twelve of 62 (19.4%) Borrelia-infected I. affinis from the Mid-Atlantic region were co-infected with Bbss and B. carolinensis. Our data support the notion that Bbsl species are maintained in largely independent enzootic cycles, with occasional spill-over resulting in multiple Bbsl species detected in Ixodes species ticks., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier GmbH.)