Background: This study tested the hypothesis that exendin-4 and sitagliptin can effectively protect kidney from acute ischemia-reperfusion (IR) injury. Methods: Adult SD-rats (n = 48) equally divided into group 1 (sham control), group 2 (IR injury), group 3 [IR + sitagliptin 600 mg/kg at post-IR 1, 24, 48 hr)], and group 4 [IR + exendin-4 10 μm/kg at 1 hr after procedure] were sacrificed after 24 and 72 hrs (n = 6 at each time from each group) following clamping of bilateral renal pedicles for 60 minutes (groups 2–4). Results: Serum creatinine level and urine protein to creatinine ratio were highest in group 2 and lowest in group 1 (all p < 0.001) without notable differences between groups 3 and 4. Kidney injury score, expressions of inflammatory biomarkers at mRNA (MMP-9, TNF-α, IL-1β, PAI-1), protein (TNF-α, NF-κB and VCAM-1), and cellular (CD68+) levels in injured kidneys at 24 and 72 hr showed an identical pattern compared to that of creatinine level in all groups (all p < 0.0001). Expressions of oxidized protein, reactive oxygen species (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP), and DNA damage marker (γH2AX+) of IR kidney at 24 and 72 hrs exhibited a pattern similar to that of inflammatory mediators among all groups (all p < 0.01). Renal expression of glucagon-like peptide-1 receptor, and anti-oxidant biomarkers at cellular (GPx, GR) and protein (NQO-1, HO-1, GPx) levels at 24 and 72 hr were lowest in group 1, significantly lower in group 2 than in groups 3 and 4 (all p < 0.01). Conclusion: Exendin-4 and sitagliptin provided significant protection for the kidneys against acute IR injury.

Aim: This study investigated the impact of the circulating galectin-3 level on the 30-day prognostic outcome in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: From May 2009 to March 2011, blood samples for assessment of the circulating galectin-3 level were collected from 196 consecutive STEMI patients treated by primary PCI and from 30 healthy volunteers. Results: The galectin-3 level was determined using ELISA. Our results demonstrated that the circulating level of galectin-3 was significantly higher in STEMI patients than in healthy control subjects (p<0.001). As compared with patients with galectin-3 <7.67 ng/mL, patients with galectin-3 ≥7.67 ng/mL were significantly older, had significantly lower left ventricular ejection fraction and significantly higher frequency of elevated white blood cell count, advanced Killip score (defined as ≥ score 3), congestive heart failure (defined as ≥ New York Heart Association Functional Class III), respiratory failure, unstable hemodynamics requiring a mechanical ventilator and intra-aortic balloon pump support, multiple vessel diseases and 30-day mortality (all p<0.04). Furthermore, multivariate analysis showed that elevated circulating level of galectin-3 was the strongest independent predictor of the combined 30-day major adverse clinical outcome (MACO) (defined as advanced CHF or 30-day mortality) (p<0.0001). Conclusion: A high circulating galectin-3 level may serve as a useful biomarker for predicting 30-day MACO in patients with STEMI undergoing primary PCI.

Objectives: To investigate the safety, feasibility, and possible adverse events of single-dose human umbilical cord-derived mesenchymal stem cells in patients with moderate-to-severe acute respiratory distress syndrome. Design: Prospective phase I clinical trial. Setting: Medical center in Kaohsiung, Taiwan. Patients: Moderate-to-severe acute respiratory distress syndrome with a Pao ₂/Fio ₂ ratio less than 200. Interventions: Scaling for doses was required by Taiwan Food and Drug Administration as follows: the first three patients received low-dose human umbilical cord-derived mesenchymal stem cells (1.0 × 10⁶ cells/kg), the next three patients with intermediate dose (5.0 × 10⁶ cells/kg), and the final three patients with high dose (1.0 × 10⁷ cells/kg) between December 2017 and August 2019. Measurements and Main Results: Nine consecutive patients were enrolled into the study. In-hospital mortality was 33.3% (3/9), including two with recurrent septic shock and one with ventilator-induced severe pneumomediastinum and subcutaneous emphysema. No serious prespecified cell infusion-associated or treatment-related adverse events was identified in any patient. Serial flow-cytometric analyses of circulating inflammatory biomarkers (CD14⁺CD33⁺/CD11b+CD16+/CD16+MPO+/CD11b+MPO+/CD14^dimCD33+) and mesenchymal stem cell markers (CD26+CD45–/CD29+CD45–/CD34+CD45–/CD44+CD45–/CD73+CD45–/CD90+CD45–/CD105+CD45–/CD26+CD45–) were notably progressively reduced (p for trend < 0.001), whereas the immune cell markers (Helper-T-cell^CD3+CD4+/Cytotoxity-T-cell^CD3+CD8+/Regulatory-T-cell^{CD4+CD25+FOXp3+}) were notably increased (p for trend < 0.001) after cell infusion. Conclusions: The result of this phase I clinical trial showed that a single-dose IV infusion of human umbilical cord-derived mesenchymal stem cells was safe with favorable outcome in nine acute respiratory distress syndrome patients.