Pulmonary pharmacology & therapeutics最新文献

{"title":"Impact of beta blockers on resting respiratory rate in older adults: A cross-sectional study","authors":"Atsushi Takayama ,&nbsp;Takashi Yoshioka ,&nbsp;Takahiko Nagamine","doi":"10.1016/j.pupt.2022.102186","DOIUrl":"10.1016/j.pupt.2022.102186","url":null,"abstract":"<div><p>[Purpose] Beta blockers, commonly prescribed for older adults, affect heart rates and blood pressure and may reduce respiratory rates, which are used to evaluate patient status and predict outcomes. However, limited clinical evidence is available on the impact of beta blockers on respiratory rates. This study aimed to investigate the impact of beta blockers on respiratory rates in older adults.</p><p><span>[Methods] This cross-sectional study included patients aged ≥60 years who underwent an annual checkup. Patients were excluded if they had a diagnosis of severe heart failure, chronic obstructive pulmonary disease, </span>interstitial pneumonitis<span>, severe anemia, or neurodegenerative disease. Doubly robust estimation with inverse probability weighting was applied to estimate the mean differences between beta blocker users and non-users. The dose-response relationship between the administered beta blockers and respiratory rates was examined using multivariable regression models.</span></p><p>[Results] Of 637 participants, 108 had received beta blockers regularly. The adjusted mean differences (95% confidence interval, CI) in respiratory rates, pulse rates, systolic blood pressure<span>, and diastolic blood pressure<span> between beta blocker users and non-users were 0.35 (−0.68 to 1.37), −3.56 (−6.34 to −0.78), −5.53 (−8.53 to −2.52), and −4.70 (−8.27 to −1.14), respectively. The adjusted mean differences (95% CI) in respiratory rates per 1 mg of a carvedilol equivalent dose in all beta blocker users, liposoluble beta blocker users, and carvedilol users were −0.10 (−0.18 to −0.02), −0.35 (−0.59 to −0.11), and −0.29 (−0.54 to −0.06), respectively.</span></span></p><p>[Conclusions] Beta blockers may dose-dependently reduce the respiratory rates of older adults. However, in clinical settings, the impact of beta-blocker use or non-use on the respiratory rate may not occur at a clinically important level. Clinicians should note the potentially suppressive impact of beta blockers on respiratory rates according to the situation.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"78 ","pages":"Article 102186"},"PeriodicalIF":3.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9124972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-sitosterol targets glucocorticoid receptor to reduce airway inflammation and remodeling in allergic asthma","authors":"Jianfeng Xu ,&nbsp;Lei Yang ,&nbsp;Tiantian Lin","doi":"10.1016/j.pupt.2022.102183","DOIUrl":"10.1016/j.pupt.2022.102183","url":null,"abstract":"<div><h3>Introduction</h3><p>In most asthma patients, symptoms are controlled by treatment<span> with glucocorticoid<span>, but long-term or high-dose use can produce adverse effects. Therefore, it is crucial to find new therapeutic strategies. β-sitosterol could suppress type Ⅱ inflammation in ovalbumin (OVA)-induced mice, but its mechanisms have remained unclear.</span></span></p></div><div><h3>Methods</h3><p><span><span><span>A binding activity of β-sitosterol with </span>glucocorticoid receptor<span> (GR) was analyzed by molecular docking. Human bronchial epithelial cells (BEAS-2B) and human bronchial </span></span>smooth muscle cells<span> (HBSMC) were treated with different concentrations (0, 1, 5, 10, 20, and 50 μg/mL) of β-sitosterol for suitable concentration selection. In transforming growth factor (TGF)-β1 treated BEAS-2B and HBSMC, cells were treated with 20 μg/mL β-sitosterol or dexamethasone (Dex) to analyze its possible mechanism. In OVA-induced mice, 2.5 mg/kg β-sitosterol or Dex administration was performed to analyze the therapeutic mechanism of β-sitosterol. A </span></span>GR antagonist<span><span> RU486 was used to confirm the mechanism of β-sitosterol in the </span>treatment of asthma.</span></p></div><div><h3>Results</h3><p><span>A good binding of β-sitosterol to GR (score = −8.2 kcal/mol) was found, and the GR expression was upregulated with β-sitosterol dose increase in BEAS-2B and HBSMC. Interleukin (IL)-25 and IL-33 secretion was significantly decreased by β-sitosterol in the TGF-β1-induced BEAS-2B, and the levels of collagen 1A and α-smooth muscle actin (SMA) were reduced in the TGF-β1-induced HBSMC. In the OVA-challenged mice, β-sitosterol treatment improved airway inflammation and remodeling through suppressing type Ⅱ immune response and collagen deposition. The therapeutic effects of β-sitosterol were similar to Dex treatment </span><em>in vitro</em> and <em>in vivo.</em> RU486 treatment clearly hampered the therapeutic effects of β-sitosterol in the TGF-β1-induced cells and OVA-induced mice.</p></div><div><h3>Conclusion</h3><p><span>This study identified that β-sitosterol binds GR to perform its functions in asthma treatment. β-sitosterol represent a potential therapeutic drug for </span>allergic asthma.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"78 ","pages":"Article 102183"},"PeriodicalIF":3.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9194438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an inhaled anti-TSLP therapy for asthma","authors":"Paul M. O'Byrne ,&nbsp;Reynold A. Panettieri Jr. ,&nbsp;Christian Taube ,&nbsp;Caterina Brindicci ,&nbsp;Margaret Fleming ,&nbsp;Pablo Altman","doi":"10.1016/j.pupt.2022.102184","DOIUrl":"10.1016/j.pupt.2022.102184","url":null,"abstract":"<div><p><span>Thymic stromal lymphopoietin<span><span><span> (TSLP), an epithelial cell-derived cytokine, acts as a key mediator in airway inflammation and modulates the function of multiple cell types, including dendritic cells and group 2 innate </span>lymphoid cells<span>. TSLP plays a role in asthma pathogenesis as an upstream cytokine, and data suggest that TSLP blockade with the anti-TSLP monoclonal antibody, </span></span>tezepelumab, could be efficacious in a broad asthma population. Currently approved asthma biologic therapies target allergic or </span></span>eosinophilic<span> disease and require phenotyping; therefore, an unmet need exists for a therapy that can address Type 2 (T2)-high and T2-low inflammation in asthma. All currently approved biologic treatments are delivered intravenously or subcutaneously; an inhaled therapy route that allows direct targeting of the lung with reduced systemic impact may offer advantages.</span></p><p><span>Currently in development, ecleralimab (CSJ117) represents the first inhaled anti-TSLP antibody fragment that binds soluble TSLP and prevents TSLP receptor activation, thereby inhibiting further inflammatory signalling cascades. This anti-TSLP antibody fragment is being developed for patients with severe uncontrolled asthma despite standard of care inhaled therapy. A Phase IIa proof of concept study, using allergen bronchoprovocation as a model for asthma exacerbations, found that ecleralimab was well-tolerated and reduced allergen-induced </span>bronchoconstriction in adult patients with mild asthma. These results suggest ecleralimab may be a promising, new therapeutic class for asthma treatment.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"78 ","pages":"Article 102184"},"PeriodicalIF":3.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9181570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of non-prostanoid prostacyclin receptor agonist for pulmonary hypertension: A meta-analysis","authors":"Pengwei Wang ,&nbsp;Hongyan Feng ,&nbsp;Yongli Guo ,&nbsp;Nan Wu ,&nbsp;Honglei Yin ,&nbsp;Yongxiang Zhang ,&nbsp;Sujuan Pei ,&nbsp;Jianlian Gao ,&nbsp;Yizhong Lu ,&nbsp;Yang Hu ,&nbsp;Yongheng Zhang ,&nbsp;Zhijian Deng","doi":"10.1016/j.pupt.2022.102182","DOIUrl":"10.1016/j.pupt.2022.102182","url":null,"abstract":"<div><h3>Background</h3><p>Oral non-prostanoid prostacyclin receptor<span><span> agonists therapies have been recommended for </span>pulmonary arterial hypertension in many countries.</span></p></div><div><h3>Objective</h3><p>We aimed to evaluate the specific impact of non-prostanoid prostacyclin receptor agonists on pulmonary hypertension and to explore the influence of study characteristics on results.</p></div><div><h3>Methods</h3><p>PubMed, Embase, and <span>ClinicalTrials.gov</span><svg><path></path></svg><span> were systematically searched from inception to July 12, 2022. Randomized controlled trials comparing non-prostanoid prostacyclin receptor agonists administration with placebo for treating pulmonary hypertension were included. Two researchers independently selected eligible studies, assessed the bias risk and extracted related data. RevMan5.1 was used for performing the statistical analysis and the assessment of bias risk of the enrolled studies. PROSPERO registered number CRD42022304172.</span></p></div><div><h3>Results</h3><p><span>Seven trials involving 1727 patients were included. Pooled analyses indicated non-prostanoid prostacyclin receptor agonists significantly reduced clinical worsening events (risk ratio [RR], 0.63; 95% confidence interval [CI], 0.54 to 0.74), increased 6-min walk distance (mean difference [MD], 10 m; 95% CI, 3–17 m), decreased pulmonary vascular resistance (MD, −121 dyn s/cm</span>⁵; 95% CI, −172 to −69 dyn s/cm⁵) and increased cardiac index (MD, 0.38 L/min/m²; 95% CI, 0.26–0.50 L/min/m²<span><span>) compared with the control. No significant differences in all-cause mortality (RR, 0.86; 95% CI, 0.26 to 2.78), NYHA/WHO functional class (RR, 1.16; 95% CI, 0.61 to 2.18), mean pulmonary artery pressure (MD, −0.88 mmHg; 95% CI, −2.20 to 0.44 mmHg), </span>right atrial pressure (MD, 0.66 mmHg; 95% CI, −0.59 to 1.90 mmHg) and total adverse events (RR, 1.05; 95% CI, 0.99 to 1.10) were found between non-prostanoid prostacyclin receptor agonists group and control group.</span></p></div><div><h3>Conclusion</h3><p>Non-prostanoid prostacyclin receptor agonists treatment exerted benefits on clinical worsening, pulmonary vascular resistance, and cardiac index in pulmonary hypertension patients, without increasing the incidence of total adverse events.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"78 ","pages":"Article 102182"},"PeriodicalIF":3.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10626166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of house dust mite subcutaneous immunotherapy in polysensitized children with allergic asthma","authors":"Panpan Zhang ,&nbsp;Yuanyuan Jia ,&nbsp;Zenghui Jing,&nbsp;Jinli Huang,&nbsp;Huajie Wu,&nbsp;Xin Sun","doi":"10.1016/j.pupt.2022.102187","DOIUrl":"10.1016/j.pupt.2022.102187","url":null,"abstract":"<div><h3>Introduction</h3><p><span>The aim of this study was to compare the efficacy and safety of 3 years of HDM<span> subcutaneous immunotherapy (HDM-SCIT) in </span></span>allergic asthma (AA) children with mono- and polysensitized.</p></div><div><h3>Methods</h3><p>This was a retrospective observational study, 51 AA children (aged 4–14 years) who had completed 3 years of standardized HDM-SCIT were enrolled in. Based on skin prick tests (SPT) and allergen-specific IgE antibody<span><span><span> (sIgE) test results, children were classified into two groups: the monosensitized group (n = 31) and the polysensitized group (n = 20). Total asthma symptoms score (TASS), total medication score (TMS), visual analog scale (VAS) scores, fractional exhaled </span>nitric oxide (FeNO), lung function parameters, and adverse reactions were evaluated before </span>treatment and at 6 months, 1, 2, 3 years of HDM-SCIT.</span></p></div><div><h3>Results</h3><p>In terms of effectiveness, compared to baseline, TASS, TMS, VAS, FeNO and lung function parameters were significantly improved in both groups after 3 years of HDM-SCIT (all <em>P</em> &lt; 0.05). The comparison between the two groups showed that efficacy indicators were no statistically significant difference at follow-up time points (all <em>P</em> &gt; 0.05) except PEF%pred at 6 months (<em>P</em> = 0.048). In terms of security, the number of adverse reactions in both groups also no statistical difference between the two groups (all <em>P</em> &gt; 0.05).</p></div><div><h3>Conclusion</h3><p>This study confirmed that no significant difference was observed in the clinical efficacy and safety of HDM-SCIT between mono-and polysensitized children with allergic asthma.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"78 ","pages":"Article 102187"},"PeriodicalIF":3.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9139393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients with moderate to severe COVID-19 outcomes on remdesivir according to baseline 4C mortality score","authors":"Jacob Sellers ,&nbsp;Jongwha Chang ,&nbsp;Jessica Jones ,&nbsp;Trager D. Hintze","doi":"10.1016/j.pupt.2022.102188","DOIUrl":"10.1016/j.pupt.2022.102188","url":null,"abstract":"<div><h3>Background</h3><p>Remdesivir was the first antiviral to show clinical benefit in patients with moderate-to-severe COVID-19. Previous trials demonstrated a faster time to recovery in hospitalized patients treated with remdesivir vs placebo. Current guidelines recommend treatment with remdesivir based on hospitalization status, oxygen requirements, and time from symptom onset. However, other factors may be evaluated to determine disease severity and risk for progression. The 4C mortality score is a validated, eight variable score that may be used to categorize patients by mortality risk at the time of hospital admission for COVID pneumonia. The objective of this study was to determine if the 4C mortality score may be used to predict which patients with moderate to severe COVID-19 would benefit the most from remdesivir at the time of hospital admission.</p></div><div><h3>Methods</h3><p>This was a single-center retrospective cohort study comparing time to recovery among hospitalized patients with moderate-to-severe COVID-19 who were treated with remdesivir compared to those who were treated with standard of care (SOC). The primary outcome was time to recovery, defined as discharge from the hospital or no longer requiring supplemental oxygen, stratified by the 4C mortality score risk group. Secondary outcomes included in-hospital mortality, hospital length of stay, and time to recovery in patients who were started on remdesivir within 7 days from symptom onset vs after 7 days from symptom onset. A survival analysis was used to analyze time to recovery outcomes.</p></div><div><h3>Results</h3><p>Data was collected and analyzed for a total of 300 patients, of which 200 received remdesivir and 100 received SOC. Patients in the remdesivir group had a longer time to recovery compared to patients in the SOC group (6 days vs 4 days). This finding was driven by patients who were categorized to the intermediate risk and high risk mortality groups. Additionally, patients who received remdesivir had a longer length of hospital stay compared to those who received SOC (12 days vs 9 days). Remdesivir was not associated with an increased rate of adverse events.</p></div><div><h3>Conclusions</h3><p>This study of patients admitted with moderate-to-severe COVID-19 found that patients who were treated with remdesivir had a longer time to recovery and a longer length of stay compared to those who received SOC. These findings add to the body of evidence questioning the benefit of remdesivir therapy among patients hospitalized with COVID-19.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"78 ","pages":"Article 102188"},"PeriodicalIF":3.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9806928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9196148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic lncRNA MALAT-1 recruits E2F1 to upregulate RAD51 expression and thus promotes cell autophagy and tumor growth in non-small cell lung cancer.","authors":"Rui Xin, Boqi Hu, Danhua Qu, Dawei Chen","doi":"10.1016/j.pupt.2023.102199","DOIUrl":"10.1016/j.pupt.2023.102199","url":null,"abstract":"<p><strong>Introduction: </strong>LncRNA MALAT-1 expression is involved in regulating activities of non-small-cell lung cancer (NSCLC) cells. This study aimed to investigate the effects of lncRNA MALAT-1 on chemosensitivity of NSCLC cells by regulating autophagy.</p><p><strong>Methods: </strong>We first validated the expression of lncRNA MALAT-1 in NSCLC cell lines. NSCLC cell lines with high lncRNA MALAT-1 expression were exposed to doxorubicin (DOX) to assess chemosensitivity. Further LncMAP database retrieval and ChIP, RIP and luciferase activity assays were conducted to explore interplay between lncRNA MALAT-1, RAD51, and E2F1. Immunofluorescence staining was performed to evaluate formation of autophagosomes in NSCLC cells. Ectopic expression and knockdown methods were used for in vitro mechanism experiments and in vivo substantiation.</p><p><strong>Results: </strong>LncRNA MALAT-1 was overexpressed in NSCLC cells, and could promote NSCLC cell autophagy and inhibit its chemosensitivity. In vitro cell mechanism verification experiments showed that lncRNA MALAT-1 could recruit transcription factor E2F1 to bind to the promoter of RAD51, so as to promote the transcriptional expression of RAD51. In addition, cell function experiments in vitro showed that ectopically expressed lncRNA MALAT-1 promoted NSCLC cell autophagy and inhibited its chemosensitivity, while RAD51 knockdown negated its effect. Finally, in vivo animal experiments confirmed that lncRNA MALAT-1 silencing could impede the tumor growth.</p><p><strong>Conclusions: </strong>Taken together, this study revealed that silencing lncRNA MALAT-1 enhanced chemosensitivity of NSCLC cells by promoting autophagy, highlighting a feasible approach to prevent chemoresistance in NSCLC treatment.</p>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":" ","pages":"102199"},"PeriodicalIF":3.2,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10612723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of house dust mite subcutaneous immunotherapy in polysensitized children with allergic asthma.","authors":"Panpan Zhang, Yuanyuan Jia, Z. Jing, Jinli Huang, Huajie Wu, Xin Sun","doi":"10.2139/ssrn.4249980","DOIUrl":"https://doi.org/10.2139/ssrn.4249980","url":null,"abstract":"INTRODUCTION\u0000The aim of this study was to compare the efficacy and safety of 3 years of HDM subcutaneous immunotherapy (HDM-SCIT) in allergic asthma (AA) children with mono- and polysensitized.\u0000\u0000\u0000METHODS\u0000This was a retrospective observational study, 51 AA children (aged 4-14 years) who had completed 3 years of standardized HDM-SCIT were enrolled in. Based on skin prick tests (SPT) and allergen-specific IgE antibody (sIgE) test results, children were classified into two groups: the monosensitized group (n = 31) and the polysensitized group (n = 20). Total asthma symptoms score (TASS), total medication score (TMS), visual analog scale (VAS) scores, fractional exhaled nitric oxide (FeNO), lung function parameters, and adverse reactions were evaluated before treatment and at 6 months, 1, 2, 3 years of HDM-SCIT.\u0000\u0000\u0000RESULTS\u0000In terms of effectiveness, compared to baseline, TASS, TMS, VAS, FeNO and lung function parameters were significantly improved in both groups after 3 years of HDM-SCIT (all P < 0.05). The comparison between the two groups showed that efficacy indicators were no statistically significant difference at follow-up time points (all P > 0.05) except PEF%pred at 6 months (P = 0.048). In terms of security, the number of adverse reactions in both groups also no statistical difference between the two groups (all P > 0.05).\u0000\u0000\u0000CONCLUSION\u0000This study confirmed that no significant difference was observed in the clinical efficacy and safety of HDM-SCIT between mono-and polysensitized children with allergic asthma.","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"1 1","pages":"102187"},"PeriodicalIF":3.2,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44977180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considerations into pharmacogenomics of COVID-19 pharmacotherapy: Hope, hype and reality","authors":"Anmar AL-Taie ,&nbsp;Ayşe Şeyma Büyük ,&nbsp;Semra Sardas","doi":"10.1016/j.pupt.2022.102172","DOIUrl":"10.1016/j.pupt.2022.102172","url":null,"abstract":"<div><p>COVID-19 medicines, such as molnupiravir are beginning to emerge for public health and clinical practice. On the other hand, drugs display marked variability in their efficacy and safety. Hence, COVID-19 medicines, as with all drugs, will be subject to the age-old maxim “one size prescription does not fit all”. In this context, pharmacogenomics is the study of genome-by-drug interactions and offers insights on mechanisms of patient-to-patient and between-population variations in drug efficacy and safety. Pharmacogenomics information is crucial to tailoring the patients' prescriptions to achieve COVID-19 preventive and therapeutic interventions that take into account the host biology, patients’ genome, and variable environmental exposures that collectively influence drug efficacy and safety. This expert review critically evaluates and summarizes the pharmacogenomics and personalized medicine aspects of the emerging COVID-19 drugs, and other selected drug interventions deployed to date. Here, we aim to sort out the hope, hype, and reality and suggest that there are veritable prospects to advance COVID-19 medicines for public health benefits, provided that pharmacogenomics is considered and implemented adequately. Pharmacogenomics is an integral part of rational and evidence-based medical practice. Scientists, health care professionals, pharmacists, pharmacovigilance practitioners, and importantly, patients stand to benefit by expanding the current pandemic response toolbox by the science of pharmacogenomics, and its applications in COVID-19 medicines and clinical trials.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"77 ","pages":"Article 102172"},"PeriodicalIF":3.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10397627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SRSF1 promotes ASMC proliferation in asthma by competitively binding CCND2 with miRNA-135a","authors":"Ya-li Guo ,&nbsp;Zhuo-chang Chen ,&nbsp;Nan Li ,&nbsp;Cui-jie Tian ,&nbsp;Dong-jun Cheng ,&nbsp;Xue-yi Tang ,&nbsp;Luo-xian Zhang ,&nbsp;Xiao-yu Zhang","doi":"10.1016/j.pupt.2022.102173","DOIUrl":"10.1016/j.pupt.2022.102173","url":null,"abstract":"<div><h3>Background</h3><p><span>Asthma is an inflammatory syndrome characterized by airway hyperresponsiveness<span>, bronchial inflammation, and airway remodeling. Abnormal proliferation of </span></span>airway smooth muscle cells<span> (ASMCs) is the main pathological feature of asthma. This study investigated the function and mechanism of serine arginine-rich splicing factor 1 (SRSF1) in ASMC proliferation in asthma.</span></p></div><div><h3>Methods</h3><p><span>SRSF1 expressions in the bronchi of ovalbumin-induced asthmatic mice and IgE-treated mouse ASMCs (mASMCs) were evaluated using quantitative real-time PCR and Western blot. The localization and expression of SRSF1 in the bronchi of asthmatic mice were assessed by </span>immunohistochemistry<span>. Functionally, gain- and loss-of-function assays, flow cytometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were conducted. Mechanistically, RNA degradation<span> assay, RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter gene assays were carried out.</span></span></p></div><div><h3>Results</h3><p>SRSF1 was highly expressed in the bronchi of ovalbumin-induced asthma mice and IgE-treated mASMCs and was mainly located in the nucleus. Experiments on the function of SRSF1 showed that the silencing of SRSF1 induced the cell cycle of mASMC arrest and restrained mASMC proliferation. Investigations into the mechanism of SRSF1 revealed that SRSF1 and miR-135a are competitively bound to the 3′UTR region of Cyclin D2 (CCND2). SRSF1 overexpression repressed the degradation of CCND2 mRNA, and miR-135a negatively regulated CCND2 expression. Furthermore, SRSF1 knockdown inhibited ASMC proliferation in asthma mouse models by regulating the levels of miR-135a and CCND2.</p></div><div><h3>Conclusion</h3><p>SRSF1 knockdown repressed ASMC proliferation in asthma by regulating miR-135a/CCND2 levels.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"77 ","pages":"Article 102173"},"PeriodicalIF":3.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10710731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}