Use of human amniotic epithelial cells in mouse models of bleomycin-induced lung fibrosis: A systematic review and meta-analysis.

BACKGROUND:Idiopathic pulmonary fibrosis (IPF) urgently requires effective treatment. Bleomycin-induced lung injury models are characterized by initial inflammation and secondary fibrosis, consistent with the pathological features of IPF. Human amniotic epithelial cells (hAECs) exhibit good differentiation potential and paracrine activity and are thus ideal for cell-based clinical therapies. The therapeutic effects of hAECs on lung fibrosis are attributed to many factors. We performed a systematic review of preclinical studies investigating the treatment of pulmonary fibrosis with hAECs to provide suggestions for their clinical use. METHODS:PubMed and EMBASE were searched for original studies describing hAEC therapy in animal bleomycin-induced pulmonary fibrosis models. After quality assessments, the number and species of experimental animals, bleomycin dose, hAEC source and dosage, time and route of administration of transplanted cells in animals, and time animals were euthanized in nine controlled preclinical studies were summarized. Ashcroft scores, lung collagen contents, inflammatory cells and cytokines were quantitatively and/or qualitatively analyzed in this review. Publication bias was also assessed. RESULTS:Each of the nine preclinical studies have unique characteristics regarding hAEC use. Ashcroft scores and lung collagen contents were decreased following hAEC transplantation in bleomycin-injured mice. Histopathology was also improved in most studies following treatment with hAECs. hAECs modulated macrophages, neutrophils, T cells, dendritic cells and the mRNA or protein levels of cytokines associated with inflammatory reactions (tumor necrosis factor-α, transforming growth factor-β, interferon-γ and interleukin) in lung tissues of bleomycin-injured mice. CONCLUSIONS:hAECs alleviate and reverse the progression of bleomycin-induced lung fibrosis in mice and may represent a new clinical treatment for IPF. hAECs exert anti-inflammatory and anti-fibrotic effects by modulating macrophage, neutrophil, T cell, dendritic cell and related cytokine levels in mice with bleomycin-induced lung fibrosis. Cell generation and the route, source and timing of hAEC transplantation all determine the therapeutic effectiveness of hAECs

Use of human amniotic epithelial cells in mouse models of bleomycin-induced lung fibrosis: A systematic review and meta-analysis - Fig 4

<p>Egger’s Plots of Ashcroft Scores (A) and Lung Collagen Contents (B).</p

Use of human amniotic epithelial cells in mouse models of bleomycin-induced lung fibrosis: A systematic review and meta-analysis - Fig 3

<p><b>Funnel Plots of Ashcroft Scores (A) and Lung Collagen Contents (B).</b> SE: standard error; and SMD: standard mean difference.</p

Summary of inflammation and fibrosis.

<p>Summary of inflammation and fibrosis.</p

Included and excluded studies.

<p>Included and excluded studies.</p

Characteristics of included studies.

<p>Characteristics of included studies.</p

Prolonged vs intermittent intravenous infusion of β-lactam antibiotics for patients with sepsis: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis

Abstract Background The prolonged β-lactam antibiotics infusion has been an attractive strategy in severe infections, because it provides a more stable free drug concentration and a longer duration of free drug concentration above the minimum inhibitory concentration (MIC). We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of prolonged vs intermittent intravenous infusion of β-lactam antibiotics for patients with sepsis. Methods This study was prospectively registered on PROSPERO database (CRD42023447692). We searched EMBASE, PubMed, and Cochrane Library to identify eligible studies (up to July 6, 2023). Any study meeting the inclusion and exclusion criteria would be included. The primary outcome was all-cause mortality within 30 days. Two authors independently screened studies and extracted data. When the I 2 values < 50%, we used fixed-effect mode. Otherwise, the random effects model was used. TSA was also performed to search for the possibility of false-positive (type I error) or false-negative (type II error) results. Results A total of 4355 studies were identified in our search, and nine studies with 1762 patients were finally included. The pooled results showed that, compared with intermittent intravenous infusion, prolonged intravenous infusion of beta-lactam antibiotics resulted in a significant reduction in all-cause mortality within 30 days in patients with sepsis (RR 0.82; 95%CI 0.70–0.96; P = 0.01; TSA-adjusted CI 0.62–1.07). However, the certainty of the evidence was rated as low, and the TSA results suggested that more studies were needed to further confirm our conclusion. In addition, it is associated with lower hospital mortality, ICU mortality, and higher clinical cure. No significant reduction in 90-day mortality or the emergence of resistance bacteria was detected between the two groups. Conclusions Prolonged intravenous infusion of beta-lactam antibiotics in patients with sepsis was associated with short-term survival benefits and higher clinical cure. However, the TSA results suggested that more studies are needed to reach a definitive conclusion. In terms of long-term survival benefits, we could not show an improvement

Mesenchymal stem cell therapy for paraquat poisoning: A systematic review and meta-analysis of preclinical studies

<div><p>Background</p><p>Paraquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal stem cells (MSCs), which differentiate into multiple cell types, have generated much enthusiasm regarding their use for the treatment of several diseases. The aim of this study was to systematically review and analyze published preclinical studies describing MSC administration for the treatment of PQ poisoning in animal models to provide a basis for cell therapy.</p><p>Methods</p><p>The electronic databases PubMed and CBMdisc were searched in this systematic review and meta-analysis. The MSC treatment characteristics of animal models of PQ poisoning were summarized. After quality assessment was performed, the effects of MSC transplantation were evaluated based on the survival rate, lung wet/dry weight, fibrosis scores, oxidative stress response, and inflammatory response. Publication bias was assessed.</p><p>Results</p><p>Eleven controlled preclinical studies involving MSC transplantation in animal models of PQ poisoning were included in this review. MSC therapy improved the survival rate and reduced the lung wet/dry weight and histopathological fibrosis changes in most studies. MSCs decreased serum or plasma malondialdehyde levels in the acute phase after 7 and 14 d and increased serum or plasma superoxide dismutase and glutathione levels at the same time points. IL-1β, TNF-α and TGF-β1 levels in blood or lung tissues were decreased to different degrees by MSCs. Lung hydroxyproline was decreased by MSCs after 14 d. No obvious evidence of publication bias was found.</p><p>Conclusion</p><p>MSCs showed anti-fibrosis therapeutic effects in animal models of lung injury caused by PQ poisoning, which may be related to reduced oxidative stress and inflammatory cytokine levels. Our review indicates a potential therapeutic role for MSC therapy to treat PQ poisoning and serves to augment the rationale for clinical studies.</p></div

Mesenchymal stem cell therapy for paraquat poisoning: A systematic review and meta-analysis of preclinical studies - Fig 5

<p><b>Funnel Plot of MDA (A), SOD (B) and GSH (C) Data.</b> SE: standard error; SMD: standard mean difference.</p

Summary of the major experimental results.

<p>Summary of the major experimental results.</p