Exercise preconditioning inhibits doxorubicin-induced cardiotoxicity via YAP/STAT3 signaling.

Doxorubicin (DOX) possesses strong anti-tumor effects but is limited by its irreversible cardiac toxicity. The relationship between exercise, a known enhancer of cardiovascular health, and DOX-induced cardiotoxicity has been a focus of recent research. Exercise has been suggested to mitigate DOX's cardiac harm by modulating the Yes-associated protein (YAP) and Signal transducer and activator of transcription 3 (STAT3) pathways, which are crucial in regulating cardiac cell functions and responses to damage. This study aimed to assess the protective role of exercise preconditioning against DOX-induced cardiac injury. We used Sprague-Dawley rats, divided into five groups (control, DOX, exercise preconditioning (EP), EP-DOX, and verteporfin + EP + DOX), to investigate the potential mechanisms. Our findings, including echocardiography, histological staining, Western blot, and q-PCR analysis, demonstrated that exercise preconditioning could alleviate DOX-induced cardiac dysfunction and structural damage. Notably, exercise preconditioning enhanced the nuclear localization and co-localization of YAP and STAT3. Our study suggests that exercise preconditioning may counteract DOX-induced cardiotoxicity by activating the YAP/STAT3 pathway, highlighting a potential therapeutic approach for reducing DOX's cardiac side effects.

Safety and Feasibility of No.12a Lymph Node Dissection by Portal Vein Approach in Radical Laparoscopic Gastrectomy for Gastric Cancer.

BACKGROUND: Traditional laparoscopic No.12a lymph node dissection in radical gastrectomy for gastric cancer may damage the peripheral blood vessels, and is not conducive to the full exposure of the portal vein and the root ligation of the left gastric vein. We recommend a new surgical procedure, the portal vein approach, to avoid these problems. METHODS: 25 patients with advanced gastric cancer underwent radical laparoscopic gastrectomy and No.12a lymph node were dissected by portal vein approach, including 7 cases with total gastrectomy, 18 cases with distal gastric resection, 14 males and 11 females. Operative time, intraoperative blood loss, time to first flatus, postoperative hospital stay, number of total lymph node dissection and No.12a lymph node dissection, No.12a lymph node metastasis rate and postoperative complications were statistically observed. RESULTS: All the patients were operated successfully and No.12a lymph node were cleaned by portal vein approach. A total of 683 lymph nodes were dissected, with the average number of lymph nodes dissection and positive lymph nodes were (27.3 ± 12.7) and (3.8 ± 5.6) respectively. The average number of No.12a lymph node dissection was (2.4 ± 1.95) and the metastasis rate of No.12a lymph node was 16% (4/25). The average operation time of radical laparoscopic distal and total gastrectomy were (239.2 ± 51.4) min and (295.1 ± 27.7) min respectively. The mean intraoperative blood loss was (134.0 ± 65.7) ml, and postoperative first anal exhaust time was (2.24 ± 0.86) d. The mean time to fluid intake was (4.2 ± 1.7) d, and postoperative hospitalization time was (9.6 ± 5.0) d. Without portal vein injure, anastomotic leakage, gastrointestinal bleeding, intestinal obstruction and other complications were observed in all patient. CONCLUSION: Our results show that the laparoscopic No.12a lymph node dissection by portal vein approach for gastric cancer is safe, feasible and has certain clinical application value.

IL-15 expression increased in response to treadmill running and inhibited endoplasmic reticulum stress in skeletal muscle in rats.

Interleukin 15 (IL-15) has recently been proposed as a circulating myokine involved in glucose uptake and utilization in skeletal muscle. However, the role and mechanism of IL-15 in exercise improving insulin resistance (IR) is unclear. Here, we investigated the alteration in expression of IL-15 and IL-15 receptor α (IL-15Rα) in skeletal muscle during treadmill running in rats with IR induced by a high-fat diet (HFD) and elucidated the mechanism of the anti-IR effects of IL-15. At 20 weeks of HFD, rats showed severe IR, with increased levels of fasting blood sugar and plasma insulin, impaired glucose tolerance, and reduced glucose transport activity. IL-15 immunoreactivity and mRNA level in gastrocnemius muscle were decreased markedly as compared with controls. IL-15Rα protein and mRNA levels in both soleus and gastrocnemius muscle were significantly decreased, which might attenuate the signaling or secretion of IL-15 in muscle. Eight-week treadmill running completely ameliorated HFD-induced IR and reversed the downregulated level of IL-15 and IL-15Rα in skeletal muscle of HFD-fed rats. To investigate whether IL-15 exerts its anti-IR effects directly in muscle, we pre-incubated muscle strips with the endoplasmic reticulum stress (ERS) inducer dithiothreitol (DTT) or tunicamycin (Tm); IL-15 treatment markedly decreased the protein expression of the ERS markers 78-kDa glucose-regulated protein, 94-kDa glucose-regulated protein and C/EBP homologous protein and inhibited ERS induced by DTT or Tm. Therefore, treadmill running promoted skeletal IL-15 and IL-15Rα expression in HFD-induced IR in rats. The inhibitory effect of IL-15 on ERS may be involved in improved insulin sensitivity with exercise training.