Biomedical Science

Andrew Natera, Andrewnatera99@gmail.com
University of Texas Health San Antonio, with Dr. Shiqi Zhang, Dr. Soumya Maity, Dr. Kumar Sharma

Sodium-Glucose Cotransporter-2 Regulates MTAP-Mediated Adenine Production in Kidney Proximal Tubular Epithelial Cells
Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors have emerged as a promising therapy for diabetic kidney disease (DKD) by reducing glucose reabsorption in the proximal tubule. Recent evidence implicates endogenous adenine accumulation as a key driver of DKD, with methylthioadenosine phosphorylase (MTAP) identified as a major source of adenine production in type 2 diabetes. Wehypothesized that SGLT2 inhibition attenuates MTAP-mediated adenine synthesis under diabetic conditions, thereby mitigating downstream pathogenic signaling. To test this, we performed western blotanalysis in MTAP knockdown and overexpressing mouse proximal tubule epithelial (MCT) cells to assess mTORCl activation and fibrotic marker expression. Single-cell spatial metabolomics using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was employed toevaluate the impact of SGLT2 inhibition on MTAP-driven adenine production. MTAP knockdownsuppressed high glucose (HG)-induced mTORCl activation and fibronectin expression, while MTAP overexpression enhanced both responses. Spatial metabolomics confirmed that dapagliflozin treatment significantly reduced HG­ induced adenine accumulation in human proximal tubule epithelial (HK-2) cells. Additionally, MTAP deletion via Adeno-Cre in tubular cells from MTAP"fl/fl mice blocked HG-induced adenine elevation. These findings demonstrate that MTAP­ mediated adenine production activates mTORCl signaling and contributes to DKD pathogenesis. SGLT2 inhibition mitigates thispathway by reducing MTAP­ derived adenine synthesis. Future studies will focus on assessing the therapeutic potential of proximal tubule-specific MTAP deletion in mouse models of DKD.
 

Kaitlyn Rojas, kaitlyn_rojas1@baylor.edu
Baylor University, with Dr. Jacques Nguyen

Glucagon-Like Peptide-1 Receptor Agonist, Semaglutide, Attenuates Self-Administration of Intravenous Fentanyl in Female Wistar rats
To address the surge of fentanyl-related overdoses and deaths, the investigation of potential treatments for opioid addiction and dependence is of the utmost importance to public health. In this study, we examined the effects of semaglutide in altering motivation using a rodent model of fentanyl addiction. Female Wistar rats (N=32) were surgically implanted with jugular vein catheters were trained to self-administer intravenous fentanyl under short (1-hour) or extended (8-hours) access conditions using fixed-ratio 1 (FR1) schedule of reinforcement. Following 21 sessions of FR1, animals were injected with semaglutide (0.1 mg/kg, s.c.) or vehicle (0.9% saline). Then, the animals began a progressive ratio (PR) schedule of reinforcement where they were tested on 0 to 10 µg/kg/inf doses of fentanyl. Lastly, a group of rats were tested using an ascending dose-response procedure to characterize the effects of semaglutide (0-0.1 mg/kg, s.c.) on self-administration behavior using a FR1 schedule of reinforcement. The results confirmed that daily semaglutide administration decreased body weights in female rats. Semaglutide (0.1 mg/kg, s.c.) significantly decreased the number of fentanyl infusions in rats previously trained under short- and long-access conditions (p<0.05). Semaglutide significantly decreased PR breakpoints at all doses of fentanyl, suggesting decreased motivation for fentanyl-seeking (p<0.05). Overall, these data further suggest that glucagon-like peptide-1 receptor agonists, including semaglutide, may modulate opioid reward signaling and invite further investigation into semaglutide as a potential therapeutic agent for opioid use.

Ruth Gelista, Ruth_Gelista1@baylor.edu
Baylor University, with Dr. Mariana Giassetti

The Effects of Cisplatin on Mice Fertility
Within the last 45 years, there has been an increase in male infertility globally.

Additionally, there is an increase in younger men diagnosed with reproductive cancers, adding to the infertility crisis due totreatment with gonadotoxic drugs, like Cisplatin. Furthermore, the effects on the individual stages of spermatogenesis are not currently well understood. This often has negative consequences for the men who survive cancer because it plays a large role in how they choose to build a family, adding more stress to a life-altering diagnosis.

The goal of the study was to assign various treatment regimens of Cisplatin to mice groups to analyze the effect onspermatogenesis stages, as well as test if recovery periods allow for recovered fertility after treatment. The main question was if mice were allowed to recover after treatment with PBS, then they would be more likely to have intact spermatocytes and spermatids, increasing their chances to produce viable offspring. Mice were assigned to one of five treatment groups: PBS, CIS/PBS, CIS, CIS/REC and CIS/CIS. The PBS was the control group, and the remaining groups were treated with Cisplatin with varying extents. Remaining mice were allowed to recover through PBS treatment after chemotherapy(CIS/PBS). Other mice were treated with Cisplatin and then euthanized to investigate the effects with no recovery period.The final group underwent two rounds of Cisplatin treatment with no recovery period in between. The next step would beimmunostaining to confirm statistical analysis from ImageJ.