PTX prodrug (University of Oklahoma Health Sciences Center)

This study evaluated the effects of oral pentoxifylline on testicular biometry, histology, and gene expression in stallions subjected to scrotal heat stress. Fourteen stallions were divided into three groups: Control (CRL, n = 4), Testicular Degeneration (DEG, n = 5), and Testicular Degeneration Treated with Pentoxifylline (DEG + PTX, n = 5). Testicular degeneration was induced by scrotal insulation, twice daily, over two consecutive days (D-1 and D0). Starting the next day (D1), oral pentoxifylline (17 mg/kg) was administered every 12 h for 30 days. Testicular biometry was measured using a caliper from D-5 to D60. On days 30 and 60, testicular biopsies were collected for histopathology and gene expression analysis of BAX, CASP8, CASP9, FAS, HSF1, and PTGS2 using RT-qPCR. Pentoxifylline reduced histological damage, with the DEG + PTX group showing less pronounced basal lamina undulation and seminiferous tubule atrophy compared to the DEG group. However, it did not fully prevent lesions like germ cell vacuolization, which was reflected macroscopically by a reduction in testicular volume in both degenerated groups. The protective effects of pentoxifylline on testicular tissue can be attributed to its ability to reduce BAX expression, prevent CASP8 and CASP9 activation, and promote cellular protective mechanisms through HSF1 activation at D30. These results highlight pentoxifylline's potential as a therapeutic agent for equine testicular damage due to scrotal heat stress, suggesting the need for further research on optimal dosage and treatment duration.

Primary malignant bone tumor is a disease that can lead to death. The usually applied clinical treatment strategy is surgical resection of the primary tumor. However, tumor cells are difficult to clean up, easy to make the tumor recurrence, and the bone defect caused by surgical resection also hindered the postoperative recovery.

Herein, in this work, mesoporous hydroxyapatite (HA) coating with petal-structure was prepared on titanium (Ti) implant surfaces by micro-arc oxidation (MAO) to accelerate the bone growth, and then paclitaxel (PTX) loaded lignin nanospheres were deposited into the HA coatings to get a sustained release for killing residual tumor cells.

The results showed that many gaps and holes of micro-scale were formed in the petal-structured HA coatings, they worked as traps for the PTX loaded nanospheres to enhance the deposited amount and immobilization stability, playing good role of drug loading platform. The encapsulation of PTX by lignin ensured a lower release rate and a higher sustaining release time when compared with the PTX without encapsulation. In addition, the HA coating with PTX loaded lignin nanospheres showed higher killing effect to tumor cells than to osteoblast.

The mesoporous HA coating with paclitaxel loaded lignin nanospheres endowed the titanium surface with good biological property and tumor cell-killing effect, so the obtained Ti-based material had a highly hopeful application as the localized implant for therapy of primary malignant bone tumor.