Biology subjects

Heralde, F. M.

Publications and source records attributed to Heralde, F. M..

3 recordsLinked to original sources

bioRxiv2025

Acute oral toxicity and angiotensin-converting enzyme (ACE) inhibitory activity of the aqueous fractions of the methanol leaf extract of Psychotria luzoniensis

This study investigated the acute oral toxicity, in vitro angiotensin-converting enzyme (ACE) inhibitory activity, and metabolite profile of the aqueous fraction of the methanol leaf extract of Psychotria luzoniensis (PLAF), a plant endemic to the Philippines. ACE inhibition was evaluated in the crude extract, fractions, and sub-fractions through IC50 determination. The most bioactive fraction was further subjected to acute oral toxicity testing in mice at the limit dose of 2000 mg/kg body weight, while metabolite profiling was performed using UHPLC-QTOF-MS/MS. PLAF exhibited the strongest ACE inhibition (IC50 34.38 {+/-} 1.86 {micro}g/ml), prompting subsequent fractionation. Among the sub-fractions (PLAF-1A - 1E), PLAF-1D demonstrated the most potent activity (IC50 9.70 {+/-} 0.10 {micro}g/ml). Acute toxicity evaluation of PLAF revealed no mortality, behavioral abnormalities, or significant alterations in body weight, organ weights, serum biochemical parameters (SGPT, SGOT, BUN, creatinine, LDH), or histopathological changes in the liver, kidney, and heart. These findings indicate an LD50 greater than 2000 mg/kg. Metabolite profiling showed candidate flavonoids previously associated with ACE inhibition, including quercetin, kaempferol, rutin, and hyperin. Other putative compounds detected include 4-(3,4-dihydroxyphenyl)-7-hydroxy-2-oxo-2H-chromen-5-yl-{beta}-D-glucopyranoside, juncein, and butin which are rarely reported in other Psychotria species. In this study, the ACE inhibitory activity and favorable toxicity profile of P. luzoniensis highlight its pharmacological potential to support further isolation of bioactive compounds and in vivo blood pressure studies.

pharmacology and toxicology↗

bioRxiv2023

Gold Nanoparticles for Monitoring of Mesenchymal Stem Cell-Loaded Bioresorbable Polymeric Wraps for Arteriovenous Fistulas

BackgroundTo address high rates of arteriovenous fistula (AVF) failure, a mesenchymal stem cell (MSC)-seeded polymeric perivascular wrap has been developed to reduce neointimal hyperplasia (NIH) and enhance AVF maturation in a rat model. However, the wraps radiolucency makes its placement and integrity difficult to monitor. PurposeIn this study, we infused gold nanoparticles (AuNPs) into the polymeric perivascular wrap to improve its radiopacity and tested the effect of infusion on the previously reported beneficial effects of the polymeric wrap on the AVF outflow vein. Materials and MethodsWe fabricated a polymeric perivascular wrap made of polycaprolactone (PCL) infused with AuNPs via electrospinning. Sprague-Dawley rat mesenchymal stem cells (MSCs) were seeded on the surface of the wraps. We then compared the effect of five AVF treatments--no perivascular wrap (i.e., control), PCL wrap, PCL+MSC wrap, PCL-Au wrap, and PCL-Au+MSC wrap--on AVF maturation in a Sprague-Dawley rat model of chronic kidney disease (n=3 per group). Statistical significance was defined as p<.05, and one-way analysis of variance was performed using GraphPad Prism software. ResultsOn micro-CT, AuNP-infused wraps demonstrated significantly higher radiopacity compared to wraps without AuNPs. On ultrasonography, wraps with and without AuNPs equally reduced the wall-to-lumen ratio of the outflow vein, a marker of vascular stenosis. On histomorphometric analysis, wraps with and without AuNPs equally reduced the neointima-to- lumen ratio of the outflow vein, a measure of NIH. On immunofluorescence analysis, representative MSC-seeded wraps demonstrated reduced neointimal staining for markers of smooth muscle cells (-SMA), inflammatory cells (CD45), and fibroblasts (vimentin) infiltration when compared to control and wraps without MSCs. ConclusionGold nanoparticle infusion allows the in vivo monitoring via micro-CT of a mesenchymal stem cell-seeded polymeric wrap over time without compromising the benefits of the wrap on arteriovenous fistula maturation. Summary StatementGold nanoparticle infusion enables in vivo monitoring via micro-CT of the placement and integrity over time of mesenchymal stem cell-seeded polymeric wrap supporting arteriovenous fistula maturation. Key ResultsO_LIGold nanoparticle (AuNP)-infused perivascular wraps demonstrated higher radiopacity on micro-CT compared with wraps without AuNPs after 8 weeks. C_LIO_LIAuNP-infused perivascular wraps equally improved the wall-to-lumen ratio of the outflow vein (a marker of vascular stenosis) when compared with wraps without AuNPs, as seen on US. C_LIO_LIAuNP-infused perivascular wraps equally reduced the neointima-to-lumen ratio of the outflow vein (a measure of neointimal hyperplasia) when compared with wraps without AuNPs, as seen on histomorphometry. C_LI

bioengineering↗

bioRxiv2022

Bioresorbable mesenchymal stem cell-loaded electrospun polymeric scaffold inhibits neointimal hyperplasia following arteriovenous fistula formation in a rat model of chronic kidney disease

In the setting of chronic kidney disease (CKD), the periadventitial injection of mesenchymal stem cells (MSCs) has shown significant potential in improving arteriovenous fistula (AVF) maturation by inhibiting neointimal hyperplasia (NIH). However, the rapid clearance of MSCs remains a challenge. Hence, we fabricated an electrospun perivascular scaffold from polycaprolactone (PCL) to support MSC attachment and allow gradual MSC elution at the outflow vein, the AVF site most prone to NIH. We performed a 5/6th nephrectomy to induce CKD in Sprague-Dawley rats, followed by direct AVF formation and perivascular scaffold application. We then compared the following groups of CKD rats: no perivascular scaffold (i.e., control), PCL scaffold, and PCL+MSC scaffold. On ultrasonography, the PCL and PCL+MSC groups showed significantly reduced wall thickness and wall-to-lumen ratio and increased luminal diameter and flow rate. Of note, the PCL+MSC group showed greater improvement in luminal diameter and flow rate compared to PCL alone. Moreover, 18F-fluorodeoxyglucose positron emission tomography showed that only PCL+MSC resulted in a significant reduction in uptake. On histology, the PCL and PCL+MSC groups showed significantly reduced neointima-to-lumen and neointima-to-media ratios and reduced neointimal CD45, -SMA, and vimentin fluorescence staining compared to the control. Although the two scaffold treatments did not differ significantly in histology, in vivo imaging suggested that the addition of MSCs promoted greater luminal expansion and blood flow and reduced the inflammatory process underlying NIH. Our results demonstrate the utility of mechanical support loaded with MSCs at the outflow vein immediately after AVF formation to support maturation by minimizing NIH.

bioengineering↗