Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine

The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h's paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3–8.9 μM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity–dependent sensors, and our protein engineering approach can be generalized to create probes for other targets.Charles A. Dana Foundation. Brain and Immuno-ImagingRaymond and Beverley Sackler FoundationNational Institutes of Health (U.S.) (grant R01-DA28299)National Institutes of Health (U.S.) (grant DP2-OD2441)National Institutes of Health (U.S.) (grant R01-GM068664)Jacobs Institute for Molecular Engineering for Medicine. Jacobs Institute for Molecular Engineering for MedicineNational Institutes of Health (U.S.) (grant R01-DE013023

Exosomes and Hair Regeneration: A Systematic Review of Clinical Evidence Across Alopecia Types and Exosome Sources

Mohammed A Al Ameer,1 Abdulaziz T Alnajim,1 Ali Al Ameer,2 Zainab Alsalman,3 Ghadeer A Al Ameer,4 Sarah T Alnajim,5 Anwar A Alghamdi,1 Raniya Moideen,4 Enas M Al Hadi6 1Department of Dermatology, Aseer Central Hospital, Abha, Saudi Arabia; 2Department of Dermatology, King Fahad Hospital Hofuf, Al-Ahsa, Saudi Arabia; 3College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia; 4College of Medicine, Almaarefa University, Riyadh, Saudi Arabia; 5College of Medicine, University of Tabuk, Tabuk, Saudi Arabia; 6Department of Dermatology, College of Medicine, Najran University, Najran, Saudi ArabiaCorrespondence: Mohammed A Al Ameer, Department of Dermatology, Aseer Central Hospital, Abha, 62217, Saudi Arabia, Tel +966566521792, Email [email protected]: Mesenchymal stem cell (MSC)-derived exosomes are recognized a promising cell-free therapy for alopecia. These nano-vesicles facilitate intercellular communication and contain a variety of bioactive molecules that can potentially stimulate hair follicle regeneration. However, the safety and efficacy of exosome therapy for alopecia remains to be determined. This systematic analysis aimed to determine the clinical safety and effectiveness of exosome therapy for hair growth, particularly androgenetic alopecia (AGA) and other forms of hair loss. Systematic searches were conducted on PubMed, Scopus, and Embase databases to find clinical studies published from inception until 10th May 2025 that explored exosome-based interventions for hair loss. Eleven studies included: two RCTs, three retrospective studies, three prospective single-arm studies, one case series, and two case reports. Extracted data included method of preparation, outcomes of hair regrowth (density, thickness, patient satisfaction), and side effects. Quality of evidence was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) levels and risk of bias tools (RoB 2 and ROBINS-I). All the studies included demonstrated improvements in at least one hair parameter, with MSC-derived exosomes from adipose tissue, placenta, hair follicles, bone marrow, foreskin, and umbilical cord having substantial increases in hair density (9.5 to 35 hairs/cm²) and hair thickness (up to 13.01 μm). Patient satisfaction was generally high (3– 10 point scales), and no serious adverse events were noted. The greatest level of evidence came from RCTs with adipose- and plant extract–derived exosome formulation. However, heterogeneity in design and outcome limited direct comparisons. Exosome therapy, particularly with MSC-derived sources, appears to be a new and safe treatment modality for hair restoration in AGA and other alopecias. The current evidence is, however, limited by heterogeneity in studies, small sample sizes, and varying follow-up durations. More well-standardized, high-quality RCTs are required to confirm these findings and establish standardized treatment protocols.Keywords: exosomes, hair regeneration, androgenetic alopecia, hair density, hair thicknes

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05-1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4-7 days or ≥ 8 days of 1.25 (1.04-1.48), p = 0.015 and 1.31 (1.11-1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care