Fibroblast growth factor 21 improves lipopolysaccharide-induced pulmonary microvascular endothelial cell dysfunction and inflammatory response through SIRT1-mediated NF-κB deacetylation.

Pneumonia is a common infectious disease of the respiratory system in children. It often leads to death in children by causing acute lung injury. Fibroblast growth factor 21 (FGF21) is a peptide hormone that plays an important role in the regulation of energy homeostasis. This study aimed to investigate the role of FGF21 in alleviating the lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cell (HPMEC) injury, as well as the underlying mechanism. The expression of sirtuin 1 (SIRT1), NF-κB p65, Ac-NF-κB p65, apoptosis-related proteins, tight junction proteins and adhesion molecules in HPMECs were analyzed by Western blotting. The viability and apoptosis of HPMECs were detected by CCK-8 and TUNEL assays. Lactate dehydrogenase level and levels of inflammatory factors were respectively determined by assay kits. The mRNA expression of adhesion molecules in HPMECs was analyzed by RT-qPCR. As a result, SIRT1 expression was decreased and the expression of NF-κB p65 and Ac-NF-κB p65 were increased in LPS-induced HPMECs, which were reversed by recombinant FGF21 (rFGF21). rFGF21 increased the viability and inhibited the apoptosis, inflammatory response, permeability, and release of cell adhesion molecules of LPS-induced HPMECs. In addition, EX527 as SIRT1 inhibitor could reverse the effect of rFGF21 on LPS-induced HPMECs. In conclusion, FGF21 improved LPS-induced HPMEC dysfunction and inflammatory response through SIRT1-mediated NF-κB deacetylation.

Community-based heat-sensitive moxibustion for primary hypertension: study protocol for a randomized controlled trial with patient-preference arms.

BACKGROUND: Low- and middle-income countries have a high prevalence of primary hypertension, but its treatment and control are often low. Heat-sensitive moxibustion (HSM), an innovative acupoint stimulation technique, may be effective for treating hypertension and thus used appropriately in primary healthcare. The objective of this study is to investigate whether HSM is effective and safe for the treatment of primary hypertension in the community. METHODS: This study is a multicenter, pragmatic, randomized controlled trial (RCT) with patient-preference arms. Four hundred patients with primary hypertension from seven communities will be enrolled. Initially, the communities will be randomly assigned into two study clusters, one using compulsory randomization and the other allowing treatment selection by patient preferences. Then, patients in the compulsory randomization cluster will be randomized to receive HSM plus their original antihypertensive regimen (HSM group) or only their original antihypertensive regimen (control group) for 6 months. Patients in the patient preference cluster may choose to receive HSM or control if they have a preference; otherwise, patients will be randomly assigned. The primary outcome is the change in systolic blood pressure from baseline; secondary outcomes include change in diastolic blood pressure, dosage of antihypertensive drugs, quality of life (QoL), severity of hypertensive symptoms, and incidence of cardiovascular events. Patient compliance with the HSM regimen, the cost-effectiveness ratio, and safety outcomes will also be evaluated. Outcome data will be collected at 6 monthly visits. DISCUSSION: This trial will provide important evidence regarding HSM as a technique for primary hypertension in primary healthcare settings. Given the randomization with patient preferences considered, the trial will also allow analyzing patient-preference effects and the comparison of randomized and nonrandomized samples, to improve the robustness and extrapolation of study conclusions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04788563 . Registered on March 9, 2021.