Daily Ards Research Analysis

BACKGROUND: Acute lung injury/Acute respiratory distress syndrome (ALI/ARDS) is a life-threatening inflammatory lung disorder characterized by high mortality rates and a lack of effective treatment options. Although mesenchymal stem cell (MSC)-based therapies have emerged as a promising approach for ARDS management, optimizing their therapeutic efficacy remains a significant challenge. Recent advances in gene modification techniques have opened new avenues for enhancing MSC functionality. Among these, Fibronectin type III domain-containing protein 5 (Fndc5)/irisin has attracted considerable attention due to its ability to improve endothelial function. This study aims to evaluate the therapeutic potential of Fndc5-modified MSCs in sepsis-induced ALI/ARDS and to elucidate the underlying molecular mechanisms driving their protective effects. METHODS: To comprehensively evaluate the therapeutic potential of Fndc5-modified MSCs (MSCs-Fndc5) in ARDS, we employed both in vivo and in vitro experimental models. In vivo, a mouse model of sepsis-induced ALI was established through intraperitoneal injection of lipopolysaccharide (LPS), and the protective effects of MSCs-Fndc5 were systematically assessed by analyzing lung histopathology, inflammatory cytokine levels, vascular endothelial integrity, lung wet-to-dry weight ratio, and MSC retention in lung tissue. In parallel, in vitro studies were conducted to investigate the role of MSCs-Fndc5 in mitigating LPS-induced endothelial cell (EC) injury, with a focus on EC proliferation, angiogenesis, barrier permeability, apoptosis, and the regulation of key signaling pathways. RESULTS: Fndc5 modification significantly increased the retention rate of MSCs in sepsis-induced ALI murine model while augmenting their in vitro proliferation and migration potential. In vivo, treatment with Fndc5-modified MSCs markedly attenuated lung inflammation, as evidenced by reduced levels of pro-inflammatory cytokines, decreased neutrophil infiltration, and improved lung histopathology. Additionally, MSCs-Fndc5 alleviated pulmonary edema, reduced fibrosis, lowered the lung wet-to-dry weight ratio, and preserved vascular endothelial integrity. In vitro, MSCs-Fndc5 significantly enhanced cell proliferation, migration, angiogenesis, endothelial barrier function, apoptosis inhibition, likely via PI3K/AKT pathway activation. CONCLUSIONS: Fndc5 overexpression in MSCs augments their therapeutic efficacy in sepsis-induced ALI/ARDS, which may be achieved by activating the endothelial PI3K/AKT pathway and improving MSCs retention in vivo. These findings propose MSCs-Fndc5 as a promising therapeutic strategy for sepsis-induced ALI/ARDS by enhancing endothelial repair, curbing inflammation, and modulating pivotal signaling pathways. Further investigation is warranted to explore the clinical applicability of MSCs-Fndc5 therapy for ARDS.

BACKGROUND: Trauma-induced acute lung injury (TALI) is a hazardous illness that requires accurate diagnosis and prompt treatment due to its high rates of morbidity and fatality. Although the biomarkers are a promising tool to support therapeutic decision-making in TALI, little is known about their effectiveness and functionality. This systematic review aims to study and synthesize the available data on these regulators used in the assessment of trauma-induced ALI. METHOD: To find relevant papers for this review, a thorough literature search was carried out across a number of databases, including PubMed, Scopus, and the Cochrane Library. The recommendations of the preferred reporting items for systematic reviews and meta-analyses (PRISMA) were adhered to. This review exclusively included experimental animal studies; therefore, all biomarker interpretations pertain to findings from animal models. RESULT: Including all available databases, the literature search yielded 3353 potentially relevant papers from PubMed (n = 3173), Scopus (n = 111), Cochrane library (n = 69). Following the exclusion of papers that did not meet the criteria, a shortlist of 16 studies was selected for the systematic review's purview. CONCLUSION: The review determines how biomarker information influences the care of TALI patients in clinical practices. This study provides significant data on the utilization of biomarkers for improving the identification of TALI, assessing disease mechanisms, and understanding factors associated with severity and outcomes. These findings contribute to the broader knowledge that may support future translational efforts aimed at improving diagnostic and prognostic approaches for this fatal condition.

BACKGROUND: Coronavirus disease 2019, is an infectious disease caused by the severe acute respiratory syndrome corona virus type-2 virus. Children affected are usually asymptomatic and those that have symptoms tend to be milder and infants are most at risk for severe disease. We describe the first two cases of coronavirus disease 2019 deaths among infants with complication of severe acute malnutrition in Sierra Leone. In the first half of June 2020, Kenema district reported first two coronavirus disease 2019 deaths of infants in Sierra Leone. We conducted a death review to understand the underlying medical conditions and predisposing factors of the deaths given the rarity of death among children with coronavirus disease 2019 disease. We describe the clinical presentation of the cases and their possible underlying medical conditions. CASE PRESENTATION: The two infant decedents were 8-month-old male and 6-month-old female Sierra Leoneans who presented with fever, vomiting, and flu-like symptoms and had complications of severe acute malnutrition and were coinfected with coronavirus disease 2019. Both patients developed severe respiratory distress which were not resolved with antibiotics and oxygen therapy. In addition, the diagnosis of coronavirus disease 2019 infection in both cases were also delayed due to low index of suspicion, and lack of treatment for coronavirus disease 2019 exacerbated their likelihood of death. CONCLUSION: The severe acute malnutrition made the infants prone to severe coronavirus disease 2019 disease and thus led to their death. We recommend community sensitization on good nutrition for infants to increase the chance of survival of children with coronavirus disease 2019 infection.