Objective To explore the effect of microRNA-381-3p(miR-381-3p)/MuRF1 axis on cardiopulmonary injury in hypoxia-induced pulmonary hypertension(HPH)mice and its potential mechanisms.Methods Sixty mice were randomly assigned to four groups:the normal control group(NC),the hypobaric hypoxia-induced pulmonary hypertension(HPH)group,the HPH+agomir control group and the HPH+miR-381-3p agomir analog group(HPH+miR-381-3p agomir),with 15 mice in each group.The HPH mouse model was established using a low-pressure and hypoxic artificial chamber.Three weeks prior to the establishment of the HPH model,miR-381-3p agomir and its corresponding control agomir were prepared by dissolving them in RNA-free phosphate-buffered saline(PBS)according to the experimental requirements.These solutions were administered via tail vein injection at a dose of 10 mg/kg,twice weekly for three consecutive weeks.Right heart function was assessed using echocardiography.Right ventricular systolic pressure(RVSP)was measured via cardiac catheterization.Pulmonary vascular remodeling was evaluated through hematoxylin and eosin(HE)staining.Levels of inflammatory cytokines in bronchoalveolar lavage fluid were quantified using enzyme-linked immunosorbent assay(ELISA).Real-time quantitative fluorescent PCR(RT-qPCR)was employed to analyze the mRNA expression levels of miR-381-3p and MuRF1.Potential targets of miR-381-3p were predicted,and pathway enrichment analysis was conducted.A dual-luciferase reporter gene assay was performed to confirm the direct regulatory effect of miR-381-3p on MuRF1.Results Compared with the NC group,the mRNA expression of miR-381-3p was significantly decreased in both the HPH group and the HPH+agomir control group,whereas the mRNA expression of MuRF1 was significantly increased(P＜0.05).In contrast,compared with the HPH group and the HPH+agomir control group,the mRNA expression of miR-381-3p was significantly increased in the HPH+miR-381-3p agomir group,while the mRNA expression of MuRF1 was significantly decreased(P＜0.05).Additionally,compared with the NC group,RVSP,right ventricular anterior wall thickness(RVAW),right ventricular hypertrophy index(RVHI),right ventricular collagen volume fraction(CVF),distal pulmonary artery wall thickness ratio(WT),pulmonary artery wall area ratio(WA),as well as IL-1β,IL-6 and TNF-α levels in alveolar lavage fluid were significantly increased in the HPH group and the HPH+agomir control group,whereas the right ventricular diameter(RVID)was significantly decreased(P＜0.05).Conversely,compared with the HPH group and the HPH+agomir control group,RVSP,RVAW,RVHI,right ventricular CVF,WT,Wa and RVID were decreased in the HPH+miR-381-3p agomir group,and IL-1β,IL-6,and TNF-α levels of alveolar lavage fluid were significantly decreased(P＜0.05).Furthermore,the downstream target genes of miR-381-3p were predicted in the database,and MuRF1 was a potential target,and the Cytoskeleton in muscle cells ranked first in the significant enrichment of target genes.Compared with WT-MuRF1+mimic control group,the luciferase activity was decreased in the WT-MuRF1+miR-381-3p mimic group(P＜0.05).There was no significant difference in the luciferase activity between the Mut-MuRF1+mimic control group and the Mut-MuRF1+miR-381-3p mimic group.Conclusion Overexpression of miR-381-3p can improve cardiopulmonary injury in HPH mice,and the mechanism may be related to the targeted inhibition of MuRF1 by miR-381-3p.

Objective To investigate the effect of naringenin(NAR)on right ventricular remodeling induced by hypoxic pulmonary hypertension(HPH)and its related mechanism.Methods SD rats were randomly divided into the control group(NC),the NC+NAR group,the HPH group and the HPH+NAR group,with 15 rats in each group.HPH model was established in a low-pressure hypoxic artificial chamber.After the successful construction of the model,rats in the NC+NAR group and the HPH+NAR group were given NAR 100 mg/(kg·d)gavage once a day for 4 weeks,while rats in the NC group and the HPH group were given the same volume of normal saline once a day for 4 weeks.Right ventricular free wall thickness(RVEDWT)and end-diastolic right ventricular diameter(RVEDD)were measured by echocardiography.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)were measured by cardiac catheter.Right ventricular mass ratio(RV/BW)and right ventricular hypertrophy index(RVHI)were calculated.Masson and Sirius staining of right ventricle was used to calculate the collagen volume fraction(CVF).TUNEL staining was used to evaluate the apoptosis of right ventricular cardiomyocytes.The contents of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in right ventricular myocardium were detected.The expression of Rho associated kinase(ROCK)protein was detected by Western blot assay.Results Compared with the NC group and the NC+NAR group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content and ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were increased in the HPH group.RVEDD and SOD activity in right ventricular myocardium were decreased(P＜0.05).Compared with the HPH group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content,ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were decreased in the HPH+NAR group,and RVEDD and SOD activity in right ventricular myocardium were increased(P＜0.05).Conclusion NAR can reduce HPH-induced right ventricular remodeling,and its mechanism may be related to inhibiting ROCK signaling pathway and further improving apoptosis and oxidative stress in right ventricular myocardium.

Objective To explore the effect of microRNA-381-3p(miR-381-3p)/MuRF1 axis on cardiopulmonary injury in hypoxia-induced pulmonary hypertension(HPH)mice and its potential mechanisms.Methods Sixty mice were randomly assigned to four groups:the normal control group(NC),the hypobaric hypoxia-induced pulmonary hypertension(HPH)group,the HPH+agomir control group and the HPH+miR-381-3p agomir analog group(HPH+miR-381-3p agomir),with 15 mice in each group.The HPH mouse model was established using a low-pressure and hypoxic artificial chamber.Three weeks prior to the establishment of the HPH model,miR-381-3p agomir and its corresponding control agomir were prepared by dissolving them in RNA-free phosphate-buffered saline(PBS)according to the experimental requirements.These solutions were administered via tail vein injection at a dose of 10 mg/kg,twice weekly for three consecutive weeks.Right heart function was assessed using echocardiography.Right ventricular systolic pressure(RVSP)was measured via cardiac catheterization.Pulmonary vascular remodeling was evaluated through hematoxylin and eosin(HE)staining.Levels of inflammatory cytokines in bronchoalveolar lavage fluid were quantified using enzyme-linked immunosorbent assay(ELISA).Real-time quantitative fluorescent PCR(RT-qPCR)was employed to analyze the mRNA expression levels of miR-381-3p and MuRF1.Potential targets of miR-381-3p were predicted,and pathway enrichment analysis was conducted.A dual-luciferase reporter gene assay was performed to confirm the direct regulatory effect of miR-381-3p on MuRF1.Results Compared with the NC group,the mRNA expression of miR-381-3p was significantly decreased in both the HPH group and the HPH+agomir control group,whereas the mRNA expression of MuRF1 was significantly increased(P＜0.05).In contrast,compared with the HPH group and the HPH+agomir control group,the mRNA expression of miR-381-3p was significantly increased in the HPH+miR-381-3p agomir group,while the mRNA expression of MuRF1 was significantly decreased(P＜0.05).Additionally,compared with the NC group,RVSP,right ventricular anterior wall thickness(RVAW),right ventricular hypertrophy index(RVHI),right ventricular collagen volume fraction(CVF),distal pulmonary artery wall thickness ratio(WT),pulmonary artery wall area ratio(WA),as well as IL-1β,IL-6 and TNF-α levels in alveolar lavage fluid were significantly increased in the HPH group and the HPH+agomir control group,whereas the right ventricular diameter(RVID)was significantly decreased(P＜0.05).Conversely,compared with the HPH group and the HPH+agomir control group,RVSP,RVAW,RVHI,right ventricular CVF,WT,Wa and RVID were decreased in the HPH+miR-381-3p agomir group,and IL-1β,IL-6,and TNF-α levels of alveolar lavage fluid were significantly decreased(P＜0.05).Furthermore,the downstream target genes of miR-381-3p were predicted in the database,and MuRF1 was a potential target,and the Cytoskeleton in muscle cells ranked first in the significant enrichment of target genes.Compared with WT-MuRF1+mimic control group,the luciferase activity was decreased in the WT-MuRF1+miR-381-3p mimic group(P＜0.05).There was no significant difference in the luciferase activity between the Mut-MuRF1+mimic control group and the Mut-MuRF1+miR-381-3p mimic group.Conclusion Overexpression of miR-381-3p can improve cardiopulmonary injury in HPH mice,and the mechanism may be related to the targeted inhibition of MuRF1 by miR-381-3p.

Objective To investigate the effect of naringenin(NAR)on right ventricular remodeling induced by hypoxic pulmonary hypertension(HPH)and its related mechanism.Methods SD rats were randomly divided into the control group(NC),the NC+NAR group,the HPH group and the HPH+NAR group,with 15 rats in each group.HPH model was established in a low-pressure hypoxic artificial chamber.After the successful construction of the model,rats in the NC+NAR group and the HPH+NAR group were given NAR 100 mg/(kg·d)gavage once a day for 4 weeks,while rats in the NC group and the HPH group were given the same volume of normal saline once a day for 4 weeks.Right ventricular free wall thickness(RVEDWT)and end-diastolic right ventricular diameter(RVEDD)were measured by echocardiography.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)were measured by cardiac catheter.Right ventricular mass ratio(RV/BW)and right ventricular hypertrophy index(RVHI)were calculated.Masson and Sirius staining of right ventricle was used to calculate the collagen volume fraction(CVF).TUNEL staining was used to evaluate the apoptosis of right ventricular cardiomyocytes.The contents of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in right ventricular myocardium were detected.The expression of Rho associated kinase(ROCK)protein was detected by Western blot assay.Results Compared with the NC group and the NC+NAR group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content and ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were increased in the HPH group.RVEDD and SOD activity in right ventricular myocardium were decreased(P＜0.05).Compared with the HPH group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content,ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were decreased in the HPH+NAR group,and RVEDD and SOD activity in right ventricular myocardium were increased(P＜0.05).Conclusion NAR can reduce HPH-induced right ventricular remodeling,and its mechanism may be related to inhibiting ROCK signaling pathway and further improving apoptosis and oxidative stress in right ventricular myocardium.

Objective To explore the effects of prohibitin 2(PHB2)on sensitivity of non-small cell lung cancer cell line A549 to erlotinib(Erl)and its potential mechanisms.Methods RACK1-specific small interfering RNA was transfected in A549 cells for knocking-down of PHB2.The effects of PHB2 inhibition on cell proliferation and apop-tosis induced by Erl were observed.The colocalization of microtuble-associated protein light chain 3 alpha(LC3)and mitochondria was visualized by MitoTracker staining and green fluorescent protein-microtuble-associated protein light chain 3 alpha(GFP-LC3)transfection.Cell proliferation was detected by 5-ethynyl-2′-deoxyuridine(EdU)staining.Cell colony formation was evaluated by colony forming assay.Apoptotic index of A549 cells was evaluated by TUNEL.Western blot was used to measure the expressions of PHB2 and LC3Ⅱ.Mitochondrial transmembrane potential,cytochrome c and respiratory chain complexⅠ/Ⅱ/Ⅴactivity were analyzed by the commercially availa-ble kits.Results Compared with the siPHB2 and siCtrl+Erl group,the EdU-positive A549 cells and the number of cell colonies decreased significantly(P＜0.05),while the TUNEL-positive A549 cells increased significantly(P＜0.05)in the siPHB2+Erl group.In addition,compared with the siPHB2 and siCtrl+Erl group,mitochondrial transmembrane potential and respiratory chain complexⅠ/Ⅱ/Ⅴactivity decreased significantly(all P＜0.05)and the levels of cytochrome c increased in mitochondrial fractions(P＜0.05)and decreased in cytosolic fractions(P＜0.05)in the siPHB2+Erl group.Conclusions PHB2 inhibition significantly improves sensitivity of A549 cells to Erl,which may be explained by inhibition of PHB2-mediated mitochondrial autophagy.

Oral and maxillofacial malignant tumors threaten the life and health of patients, and seriously affect their swallowing, language function and face. 125I seeds brachytherapy for oral and maxillofacial malignant tumors has been widely concerned and studied because of its advantages such as less surgical trauma, large and uniform dose distribution in the target tissue, little damage to the surrounding normal tissue, and reducing radiation exposure of medical staff. Low-dose brachytherapy with 125I seeds can effectively reduce the tumor volume and prolong the survival time of patients. This article reviews the clinical application of 125I seeds brachytherapy in oral and maxillofacial malignant tumors.

Objective: To observe the oral care effects of finger toothbrush. Methods: The finger toothbrush worn on the index finger was made of silica gel .It was used to brush the in vitro healthy teeth pulled out on the same day and the standard hard plaster tooth model and to brush the in vivo healthy teeth in adults; the bacteria in the finger toothbrush, The dentofacial pluque and the abrasion on the tooth model were tested respectively. Results: After in vivo use the bacteria remained in the finger toothbrush were fewer than those in the commonly used toothbrush(1 683.24?1 355.59 and 2 353.76?1 582.06 respectively). The dentofacial plaque was decreased in the same extent by the two kinds of toothbrushes. The zero rate of abrasion on the tooth model was 93.3%(28/30) by finger toothbrush and 23.3%(14/30) by the commonly used toothbrush. Conclusion: The finger toothbrush worn on finger can remove dentofacial plaque effectively and produce a lower abrasion on tooth.