Runt-related transcription factor-1(RUNX1),also known as the core-binding factor alpha 2 subunit,is closely related to human leukemia.The functions of RUNX1 in modulating cell proliferation,differentiation,and surviva...Runt-related transcription factor-1(RUNX1),also known as the core-binding factor alpha 2 subunit,is closely related to human leukemia.The functions of RUNX1 in modulating cell proliferation,differentiation,and survival in multiple systems have been gradually discovered with the emergence of transgenic mice.RUNX1 is a powerful transcription factor implicated in diverse signaling pathways and cellular mechanisms that participate in lung development and pulmonary diseases.RUNX1 has recently been identified as a target regulator of fibrotic remodeling diseases,particularly in the kidney.However,the role of RUNX1 in pulmonary fibrosis is unclear.Pulmonary fibrosis is characterized by obscure nosogenesis,limited therapy,and poor prognosis.Moreover,the population of patients with pulmonary fibrosis is gradually increasing.Thus,there is an unmet need for therapeutic targets.In this review,we retrospectively discuss the alteration in RUNX1 mRNA expression in the RNA sequencing data of human fibrotic lungs and the protein levels in mouse pulmonary fibrosis.Subsequently,we focused on the interaction between RUNX1 and several signaling pathways involved in pulmonary fibrosis.Finally,this review highlights the therapeutic potential of RUNX1 as a target for slowing the progression of fibrotic lung disease.展开更多
Benralizumab is a monoclonal antibody that targets interleukin-5 receptor α to deplete blood eosinophils and improve the clinical outcomes of allergic asthma. We conducted a meta-analysis to evaluate the safety and e...Benralizumab is a monoclonal antibody that targets interleukin-5 receptor α to deplete blood eosinophils and improve the clinical outcomes of allergic asthma. We conducted a meta-analysis to evaluate the safety and efficacy of different doses of benralizumab in patients with eosinophilic asthma. All randomized controlled trials involving benralizumab treatment for patients with eosinophilic asthma, which were searched in PubMed, Embase, and the Cochrane Library published until January 2017, as well as the rate of asthmatic exacerbation, pulmonary functionality, asthma control, quality of life scores, and adverse events were included. Randomized-effect models were used in the meta-analysis to calculate the pooled mean difference, relative risks, and 95% confidence intervals. Five studies involving 1951 patients were identified. Compared with the placebo, benralizumab treatment demonstrated significant improvements in the forced expiratory volume in 1 s （FEV1）, Asthma Quality of Life Questionnaire scores, decreased asthmatic exacerbation and Asthma Control Questionnaire-6 （ACQ-6） scores. Benralizumab treatment was also not associated with increased adverse events. These findings indicated that benralizumab can be safely used to improve FEV1, enhance patient symptom control and quality of life, and reduce the risk of exacerbations and ACQ-6 scores in patients with eosinophilic asthma. Furthermore, our meta-analysis showed that benralizumab with 30 mg （every eight weeks） dosage can improve the health-related quality of life and appear to be more effective than 30 mg （every four weeks） dosage. Overall, data indicated that the optimal dosing regimen for benralizumab was possibly 30 mg （every eight weeks）.展开更多
基金funded by 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,Grant No.ZYJC18021Post-Doctoral Research Project,West China Hospital,Grant No.2021HXBH074+1 种基金the National Natural Science Foundation of China,Grant No.82100075Sichuan Science and Technology Program,Grant Nos.2020YFH0073,2021YFG0329。
文摘Runt-related transcription factor-1(RUNX1),also known as the core-binding factor alpha 2 subunit,is closely related to human leukemia.The functions of RUNX1 in modulating cell proliferation,differentiation,and survival in multiple systems have been gradually discovered with the emergence of transgenic mice.RUNX1 is a powerful transcription factor implicated in diverse signaling pathways and cellular mechanisms that participate in lung development and pulmonary diseases.RUNX1 has recently been identified as a target regulator of fibrotic remodeling diseases,particularly in the kidney.However,the role of RUNX1 in pulmonary fibrosis is unclear.Pulmonary fibrosis is characterized by obscure nosogenesis,limited therapy,and poor prognosis.Moreover,the population of patients with pulmonary fibrosis is gradually increasing.Thus,there is an unmet need for therapeutic targets.In this review,we retrospectively discuss the alteration in RUNX1 mRNA expression in the RNA sequencing data of human fibrotic lungs and the protein levels in mouse pulmonary fibrosis.Subsequently,we focused on the interaction between RUNX1 and several signaling pathways involved in pulmonary fibrosis.Finally,this review highlights the therapeutic potential of RUNX1 as a target for slowing the progression of fibrotic lung disease.
文摘Benralizumab is a monoclonal antibody that targets interleukin-5 receptor α to deplete blood eosinophils and improve the clinical outcomes of allergic asthma. We conducted a meta-analysis to evaluate the safety and efficacy of different doses of benralizumab in patients with eosinophilic asthma. All randomized controlled trials involving benralizumab treatment for patients with eosinophilic asthma, which were searched in PubMed, Embase, and the Cochrane Library published until January 2017, as well as the rate of asthmatic exacerbation, pulmonary functionality, asthma control, quality of life scores, and adverse events were included. Randomized-effect models were used in the meta-analysis to calculate the pooled mean difference, relative risks, and 95% confidence intervals. Five studies involving 1951 patients were identified. Compared with the placebo, benralizumab treatment demonstrated significant improvements in the forced expiratory volume in 1 s （FEV1）, Asthma Quality of Life Questionnaire scores, decreased asthmatic exacerbation and Asthma Control Questionnaire-6 （ACQ-6） scores. Benralizumab treatment was also not associated with increased adverse events. These findings indicated that benralizumab can be safely used to improve FEV1, enhance patient symptom control and quality of life, and reduce the risk of exacerbations and ACQ-6 scores in patients with eosinophilic asthma. Furthermore, our meta-analysis showed that benralizumab with 30 mg （every eight weeks） dosage can improve the health-related quality of life and appear to be more effective than 30 mg （every four weeks） dosage. Overall, data indicated that the optimal dosing regimen for benralizumab was possibly 30 mg （every eight weeks）.
