Biology subjects

Jaimes, E. A.

Publications and source records attributed to Jaimes, E. A..

3 recordsLinked to original sources

bioRxiv2025

Galectin-3 is a Nanotherapeutic Target in Graft-versus-Host Disease Mediated Kidney Injury

Kidney injury is a frequent and serious complication of allogeneic hematopoietic cell transplantation (HCT), yet its pathophysiology remains poorly understood and effective treatments are lacking. Through analysis of kidney tissue from HCT recipients, we identified substantial acute tubular injury and T cell infiltration that correlated with extra-renal graft-versus-host disease (GVHD) severity, linking systemic alloreactivity and post-transplant renal pathology. In murine models, GVHD was similarly associated with acute kidney injury, renal Th1-type T cell infiltration, and hyperactivation of NF-{kappa}B and JAK-STAT signalling. Notably, galectin-3, a damage-associated lectin, was upregulated in both patient biopsies and experimental GVHD target organs. Leveraging this pathological feature, we engineered galectin-3-targeted lipid nanoparticles for tissue-specific delivery of ruxolitinib, an approved GVHD therapy. Galectin-3 upregulation was also identified in canonical acute GVHD target organs including the liver and intestinal tract, and nanoparticle-delivered ruxolitinib substantially enhanced renal function, reduced systemic GVHD, and minimized hematologic toxicity compared to conventional drug administration. Our findings demonstrate renal involvement in acute GVHD and establish a nanoparticle-based strategy for precision delivery of immunomodulatory therapies to affected tissues.

bioengineering↗

bioRxiv2021

Radiation Exposure of the Base of the Heart Accelerates Coronary Atherosclerosis

Clinical studies have identified cardiac exposure as an independent predictor for cardiovascular mortality in patients treated with radiation therapy (RT) for thoracic malignancies. Although the mechanisms are not completely understood, the available evidence indicate that direct injury to the coronary arteries endothelium is implicated. In these studies we tested the hypothesis that different areas of the heart are more sensitive to the effects of RT on the formation of atherosclerotic plaque in apolipoprotein E deficient (ApoE-/-) mice, a well validated model of atherosclerosis. MethodsApoE-/- mice on a high fat diet (HFD) received 16Gy cardiac irradiation targeted to the whole or partial (apical or basal) region of the heart at 9 weeks or 16 weeks of age. Atherosclerotic lesions and inflammatory changes in the hearts as compared to control unirradiated mice were assessed eight weeks following radiation. ResultsAfter either basal or whole heart RT at 9 weeks of age the number of subendocardial atherosclerotic lesions at the heart base was higher as compared to unirradiated mice. Irradiation of the apex did not increase the number of subendocardial atherosclerotic lesions in any region. After basal RT at 16 weeks of age the number of coronary and subendocardial atherosclerotic lesions was higher as compared to controls. Neither apical or whole heart RT had an impact on the development or acceleration of lesions in the basal region of the hearts of 16 week old mice, thus demonstrating the adverse impact of basal irradiation. Infiltration of inflammatory cells (CD45+ and CD3+) and enhanced expression of endothelial adhesion molecules (CD31), were differentially and locally regulated based upon the site of irradiation. In support of a role of eicosanoid mediators for base or whole heart atherogenic irradiation effects, apex irradiation eicosanoid mediators are not clearly atherogenic, in contrast to eicosanoid mediators detected in serum after base heart irradiation. These results indicate that the base of the heart is significantly more prone to the development of atherosclerotic lesions in the coronary arteries post-RT. ConclusionOur results indicate that the base of the heart is more susuceptible to development of RT-induced atherosclerotic lesions and therefore avoidance from RT direct exposure to this area may reduce the risk for atherosclerotic disease in patients undergoing RT.

cancer biology↗

bioRxiv2020

Edaravone-Loaded Mesoscale Nanoparticles Treat Cisplatin-Induced Acute Kidney Injury

Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. In our prior work, we developed a highly-selective kidney-targeted mesoscale nanoparticle (MNP) that accumulates primarily in the renal proximal tubular epithelial cells while exhibiting no toxicity. Here, we found that MNPs exhibit renal-selective targeting in multiple mouse models of tumor growth with virtually no tumor accumulation. We then evaluated the therapeutic efficacy of MNPs loaded with the reactive oxygen species scavenger edaravone in a mouse model of CI-AKI. We found a marked and significant therapeutic effect with this approach as compared to free drug or empty control MNPs, including improved renal function, histology, and diminution of oxidative stress. These results indicated that renal-selective MNP edaravone delivery holds substantial potential in the treatment of acute kidney injury among patients undergoing cisplatin-based chemotherapy.

bioengineering↗