A Cross-Sectional Survey on COVID-19 Vaccine Hesitancy Among Parents From Shandong vs. Zhejiang.

Introduction: With the approval of COVID-19 vaccinations for children and adolescents in China, parental vaccine hesitancy will emerge as a new challenge with regard to the administration of these vaccines. However, little is known regarding this hesitancy as well as regional differences that may exist between parents from Shandong vs. Zhejiang. Methods: To assess these issues, an online survey was conducted via a Wenjuanxing platform over the period from July 22 to August 14, 2021. Parents from Shandong and Zhejiang were recruited from Wechat groups and results from a total of 917 subjects were analyzed. Factors evaluated in this survey included socio-demographic variables, parental vaccine hesitancy, Parental Attitudes toward Childhood Vaccines (PACV) domains (behavior, safety and efficacy, general attitudes) and social support. Results: Compared with those from Shandong (N = 443), parents from Zhejiang (N = 474) showed significantly higher prevalence rates of COVID-19 vaccine hesitancy (19.4 vs. 11.7%, p = 0.001). Multivariate logistic regression showed that yearly household incomes of ≥120,000 RMB (p = 0.041), medical workers (p = 0.022) and general attitudes of PACV (p = 0.004) were risk factors for vaccine hesitancy among parents from Shandong, while behavior (p = 0.004), safety and efficacy (p < 0.001) and general attitudes of PACV (p = 0.002) were risk factors for parents from Zhejiang. Among parents with vaccine hesitancy (N = 144), concerns over side effects (91.0%) and unknown effects (84.0%) of the COVID-19 vaccine were the most prevalent reasons for hesitancy. Evidence providing proof of vaccine safety (67.4%) and assurance of a low risk of being infected by COVID-19 (60.4%) were the two most effective persuasive factors. Conclusion: Parents from Zhejiang showed a higher prevalence of COVID-19 vaccine hesitancy as compared with those from Shandong. Behavior, safety and efficacy, and general attitudes of PACV were the risk factors associated with this hesitancy in these parents from Zhejiang. Given the identification of the various reasons for parental vaccine hesitancy, different strategies as well as regional adjustments in these strategies will be required for an effective and convincing protocol for childhood vaccinations.

S1P1 receptor inhibits kidney epithelial mesenchymal transition triggered by ischemia/reperfusion injury via the PI3K/Akt pathway.

Ischemia/reperfusion (I/R) is a major cause of acute kidney injury (AKI), along with delayed graft function, which can trigger chronic kidney injury by stimulating epithelial to mesenchymal transition (EMT) in the kidney canaliculus. Sphingosine 1-phosphate receptor 1 (S1P1) is a G protein-coupled receptor that is indispensable for vessel homeostasis. This study aimed to investigate the influence of S1P1 on the mechanisms underlying I/R-induced EMT in the kidney using in vivo and in vitro models. Wild-type (WT) and S1P1-overexpressing kidney canaliculus cells were subject to hypoxic conditions followed by reoxygenation in the presence or absence of FTY720-P, a potent S1P1 agonist. In vivo, bilateral arteria renalis in wild-type mice and mice with silenced S1P1 were clamped for 30 min to obtain I/R models. We found that hypoxia/reoxygenation (H/R) significantly enhanced the expressions of EMT biomarkers and down-regulated S1P1 expression in wild-type canaliculus cells. In contrast, FTY720-P treatment or overexpression of S1P1 significantly suppressed EMT in wild-type canaliculus cells. Furthermore, after 48-72 h, a significant upregulation of EMT biomarker expression was triggered by I/R in mice with silenced S1P1, while the expressions of these markers did not change in wild-type mice. A kt activity was increased with H/R-induced EMT, suggesting that the protective influence of FTY720-P was due to its inhibition of PI3K/Akt. Therefore, the results of this study provide evidence that down-regulation of S1P1 expression is essential for the generation and progression of EMT triggered by I/R. S1P1 exhibits a prominent inhibitory effect on kidney I/R-induced EMT in the kidney by affecting the PI3K/Akt pathway.

Deguelin induces PUMA-mediated apoptosis and promotes sensitivity of lung cancer cells (LCCs) to doxorubicin (Dox).

As a natural agent for chemotherapy, deguelin remarkably suppresses proliferation in numerous solid cancers. Nevertheless, the molecular mechanisms of its suppression are still insufficient. In our research, it was revealed that deguelin induced cell death of lung cancer cells (LCCs) by triggering expression of PUMA. Deguelin triggered PUMA induction independently of p53 via suppression of PI3K/AKT pathway, therefore stimulating Foxo3a to bind with PUMA promoter and stimulate its transcription. Subsequent to activation, PUMA motivated Bax as well as the intrinsic mitochondrial cell death pathway. Removal of PUMA from LCC cells led to deguelin resistance, suggesting deguelin-induced cell death was modulated by PUMA. Furthermore, we demonstrated that deguelin enhanced the chemotherapeutic sensitivity of doxorubicin in vitro and in vivo, which were associated with potentiated PUMA induction. Taken together, these results establish a critical role of PUMA in mediating the anticancer effects of deguelin in lung cancer cells and provide the rationale for clinical evaluation.