Follow-up of Methanol-related Visual Defects in a Cohort Study: Initial Severity Predicts Long-term Outcome

Objective: Methanol poisoning can occur either intentionally through the consumption of methanol-containing products or accidentally through ingestion, resulting in visual impairment. We assessed the long-term visual sequelae in patients with methanol poisoning. Methods: This prospective cohort study was conducted at referral centers, Khorshid and Alzahra University Hospitals, affiliated with Isfahan University of Medical Sciences, Isfahan, Iran. The study included patients hospitalized for methanol poisoning from June 22, 2018, to June 21, 2020, with follow-up extended until June 2021. Toxico-clinical and ophthalmologic examination data were collected from patients upon hospital admission, discharge, and during follow-up. Findings: Thirty-nine patients were assessed in this study. The majority of them (94.9%) were male, with an average age of 34 years. Patients who presented with reduced visual acuity (VA) upon admission subsequently showed abnormalities (in acuity and visual fields) during follow-up (n = 13). Among the patients who displayed visual field defects on admission, bilateral optic disc atrophy was observed in follow-up (n = 13). Conversely, patients who reported blurred vision, with or without photophobia upon admission, had normal results in their follow-up eye examinations. Among the 36 patients who underwent dialysis, 14 (38.9%) exhibited visual impairment during follow-up examinations. Additionally, 38 patients received sodium bicarbonate, and 14 of them (36.85%) also presented ocular abnormalities. Conclusion: Patients who demonstrated VA deficits upon admission are more likely to experience long-term VA and visual field defects, as well as optic disc atrophy. Patients who solely complained of blurred vision, with or without photophobia, during admission were less likely to develop long-term visual defects

Transfection of hypoxia-inducible factor-1α mRNA upregulates the expression of genes encoding angiogenic growth factors

Abstract Hypoxia-Inducible Factor-1α (HIF-1α) has presented a new direction for ischemic preconditioning of surgical flaps to promote their survival. In a previous study, we demonstrated the effectiveness of HIF-1a DNA plasmids in this application. In this study, to avoid complications associated with plasmid use, we sought to express HIF-1α through mRNA transfection and determine its biological activity by measuring the upregulation of downstream angiogenic genes. We transfected six different HIF-1a mRNAs–one predominant, three variant, and two novel mutant isoforms–into primary human dermal fibroblasts using Lipofectamine, and assessed mRNA levels using RT-qPCR. At all time points examined after transfection (3, 6, and 10 h), the levels of HIF-1α transcript were significantly higher in all HIF-1α transfected cells relative to the control (all p < 0.05, unpaired Student’s T-test). Importantly, the expression of HIF-1α transcription response genes (VEGF, ANG-1, PGF, FLT1, and EDN1) was significantly higher in the cells transfected with all isoforms than with the control at six and/or ten hours post-transfection. All isoforms were transfected successfully into human fibroblast cells, resulting in the rapid upregulation of all five downstream angiogenic targets tested. These findings support the potential use of HIF-1α mRNA for protecting ischemic dermal flaps

Induced Pluripotent Stem Cell-Derived Extracellular Vesicles Promote Wound Repair in a Diabetic Mouse Model via an Anti-Inflammatory Immunomodulatory Mechanism

Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have recently been explored in clinical trials for treatment of diseases with complex pathophysiologies. However, production of MSC EVs is currently hampered by donor-specific characteristics and limited ex vivo expansion capabilities before decreased potency, thus restricting their potential as a scalable and reproducible therapeutic. Induced pluripotent stem cells (iPSCs) represent a self-renewing source for obtaining differentiated iPSC-derived MSCs (iMSCs), circumventing both scalability and donor variability concerns for therapeutic EV production. Thus, it is initially sought to evaluate the therapeutic potential of iMSC EVs. Interestingly, while utilizing undifferentiated iPSC EVs as a control, it is found that their vascularization bioactivity is similar and their anti-inflammatory bioactivity is superior to donor-matched iMSC EVs in cell-based assays. To supplement this initial in vitro bioactivity screen, a diabetic wound healing mouse model where both the pro-vascularization and anti-inflammatory activity of these EVs would be beneficial is employed. In this in vivo model, iPSC EVs more effectively mediate inflammation resolution within the wound bed. Combined with the lack of additional differentiation steps required for iMSC generation, these results support the use of undifferentiated iPSCs as a source for therapeutic EV production with respect to both scalability and efficacy.https://doi.org/10.1002/adhm.20230087