Renal brosis is a pathological state in the progression of chronic kidney disease. Early detection and treatment are vital to prolong the survival of patients. Renal puncture examination represents the gold standard examination method for renal brosis, but it has several limitations. This study aims to evaluate the diagnostic performance of a novel PET radiotracer, [ 68 Ga]Ga-broblast activation protein inhibitor (FAPI)-04, which speci cally images broblast activation protein (FAP) expression for renal brosis. MethodsAll patients underwent renal puncture before receiving [ 68 Ga]Ga-FAPI-04 PET/CT imaging. They then underwent [ 68 Ga]Ga-FAPI-04 PET/CT and immunochemistry examinations, and the data obtained were analyzed. ResultsThe [ 68 Ga]Ga-FAPI-04 PET/CT examination results showed that almost all patients (12/13) exhibited increased radiotracer uptake. The maximum standardized uptake value (SUVmax) in patients with mild, moderate, and severe brosis was 3.92±1.50, 5.98±1.6, and 7.67±2.23, respectively. ConclusionCompared with renal puncture examination, non-invasive imaging of FAP expression through [ 68 Ga]Ga-FAPI-04 PET/CT can quickly show the patient's bilateral kidney condition with high sensitivity. This can facilitate the evaluation of the patient's disease progression, diagnosis, and the development of a treatment plan.

Polyphenolic acids are the widely occurring natural products in almost each herbal plant, among which rosmarinic acid (RA, C18H16O8) is well-known, and is present in over 160 species belonging to many families, especially the Lamiaceae. Aside from this herbal ingredient, dozens of its natural derivatives have also been isolated and characterized from many natural plants. In recent years, with the increasing focus on the natural products as alternative treatments, a large number of pharmacological studies have been carried out to demonstrate the various biological activities of RA such as anti-inflammation, anti-oxidation, anti-diabetes, anti-virus, anti-tumor, neuroprotection, hepatoprotection, etc. In addition, investigations concerning its biosynthesis, extraction, analysis, clinical applications, and pharmacokinetics have also been performed. Although many achievements have been made in various research aspects, there still exist some problems or issues to be answered, especially its toxicity and bioavailability. Thus, we hope that in the case of natural products, the present review can not only provide a comprehensive understanding on RA covering its miscellaneous research fields, but also highlight some of the present issues and future perspectives worth investigating later, in order to help us utilize this polyphenolic acid more efficiently, widely, and safely.

Pulmonary ischemia/reperfusion (IR) injury is the leading cause of acute lung injury, which is mainly attributed to reactive oxygen species (ROS) induced cell injuries and apoptosis. Since rosmarinic acid (RA) has been identified as an antioxidant natural ester, this natural compound might protect against pulmonary IR injury. In this study, the mice were given RA daily (50, 75, or 100 mg/kg) by gavage for 7 days before the pulmonary IR injury. We found that hypoxemia, pulmonary edema, and serum inflammation cytokines were aggravated in pulmonary IR injury. RA pretreatment (75 and 100 mg/kg) effectively reversed these parameters, while 50 mg/kg RA pretreatment was less pronounced. Our data also indicated RA pretreatment mitigated the upregulation of pro-oxidant NADPH oxidases (NOX2 and NOX4) and the downregulation of anti-oxidant superoxide dismutases (SOD1 and SOD2) upon IR injury. In vitro studies showed RA preserved the viability of anoxia/reoxygenation (AR)-treated A549 cells (a human lung epithelial cell line), and the results showed the protective effect of RA started at 5 μM concentration, reached its maximum at 15 μM, and gradually decreased at 20–25 μM. Besides, RA pretreatment (15 μM) greatly reduced the lactate dehydrogenase release levels subjected to AR treatment. Moreover, the results of our research revealed that RA eliminated ROS production and reduced alveolar epithelial cell apoptosis through activating the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway, which was supported by using wortmannin, because in the presence of wortmannin, the RA-mediated protection was blocked. Meanwhile, wortmannin also reversed the protective effects of RA in mice. Together, our results demonstrate the beneficial role of RA in pulmonary IR injury via PI3K/Akt-mediated anti-oxidation and anti-apoptosis, which could be a promising therapeutic intervention for pulmonary IR injury.

Follistatin-like 1 (FSTL-1), a secreted glycoprotein, is upregulated in the serum of patients with acute kidney injury. However, it is unknown whether it protects against renal ischemia-reperfusion (I/R) injury. Our present study found that treatment with FSTL-1 (100 mg/kg) intravenous injection alleviated renal injury, as evidenced by reduced serum creatinine (Scr) and blood urea nitrogen (BUN) levels, along with reduced histopathological kidney damage. Moreover, FSTL-1 treatment reduced the number of apoptotic cells and the accumulation of reactive oxygen species (ROS) during I/R injury. The protective effect of FSTL-1 was via AMPK/PPAR-δ pathway, because, after blockade of AMPK/PPAR-δ pathway by individual inhibitor (GSK0660, a PPAR-δ antagonist, or compound C, an AMPK inhibitor), the protective effects of FSTL-1 on oxidative stress and apoptosis were blocked. Taken together, our results reveal that FSTL-1 attenuates renal I/R injury by inhibiting apoptosis in renal tubular epithelial cells, which is meditated by activating AMPK/PPAR-δ pathway.