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Background: Acute Respiratory Distress Syndrome (ARDS) is a critical complication of sepsis, associated with high morbidity and mortality. Identifying risk factors for ARDS among sepsis patients is essential for early intervention and improving outcomes. Methods: We conducted a comprehensive meta-analysis, reviewing studies that examined the association between various risk factors and ARDS development in sepsis patients. Databases such as PubMed, EMBASE, Cochrane Library, Medline, CINAHL, and Web of Science were searched up to January 2024, without language restrictions. Eligible studies included observational cohorts and case-control studies. Pooled odds ratios (ORs) and standardized mean differences (SMDs) were calculated using a random-effects model. Heterogeneity was assessed through I2 statistics, and publication bias was evaluated via the Luis Furuya-Kanamori (LFK) index. Results: 15 studies with more than 40,000 participants were analyzed. Significant risk factors for ARDS included pulmonary infection (OR: 2.696, 95 % CI: 1.655 to 4.390), septic shock (OR: 2.627, 95 % CI: 1.850 to 3.731), and pancreatitis (OR: 3.734, 95 % CI: 2.958 to 4.712). No significant associations were found between the development of ARDS in septic patients and the following risk factors: sex (OR: 1.106, 95%CI: 0.957–1.279), smoking status (OR: 1.214, 95%CI: 0.835–1.765), or steroid use (OR: 0.901, 95%CI: 0.617–1.314). APACHE-II and SOFA scores were predictive of ARDS development, emphasizing their utility in clinical assessments. Conclusion: Pulmonary infection, septic shock, and pancreatitis significantly increase ARDS risk in sepsis patients. Our findings advocate for targeted management of these risk factors to mitigate ARDS development, emphasizing the importance of personalized care in sepsis management.

Sixteen dihydroartemisinin-5-methylisatin hybrids 6a–c and 7a–m tethered via different carbon spacers were assessed for their antiproliferative activity against MCF-7, MDA-MB-231, MCF-7/ADR and MDA-MB-231/ADR breast cancer cell lines as well as cytotoxicity towards MCF-10A cells to investigate the influence of the length of carbon spacers on the activity. The preliminary results illustrated that the length of the carbon spacer was the main parameter which affected the activity, and hybrids tethered via the two-carbon linker showed the highest activity. Amongst the synthesized hybrids, the representative hybrid 7a (IC50: 15.3–20.1 µM) not only demonstrated profound activity against both drug-sensitive and drug-resistant breast cancer cell lines, but also possessed excellent safety and selectivity profile. Collectivity, hybrid 7a was a promising candidate for the treatment of both drug-sensitive and drug-resistant breast cancers and worthy of further preclinical evaluations.

miR-150 was found to target the 3′-untranslated regions of AKT3, and the AKT pathway was affected by SR protein kinase 1 (SRPK1). However, the expression and significance of miR-150, AKT3 and SRPK1 in acute lung injury (ALI) were not clear. Here, we found that the expression of miR-150 was significantly reduced, while the expression of AKT3 and SRPK1 were markedly increased in LPS-treated A549, THP-1 and RAW 264.7 cells. miR-150 significantly decreased levels of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, reduced the expression of AKT3, but had no impact on SRPK1 expression compared with the control group in LPS-treated A549, THP-1 and RAW 264.7 cells. AKT3 silencing only reduced the production of pro-inflammatory cytokines and showed no effect on miR-150 and SRPK1 expression. Finally, we observed that miR-150 mimics and/or silencing of SRPK1 decreased the expression of AKT3 mRNA. Besides, over-expression of miR-150 or silencing of SRPK1 also reduced the expression of AKT3 protein, which exhibited the lowest level in the miR-150 mimics plus si-SRPK1 group. However, si-SRPK1 had no effect on miR-150 level. In conclusion, miR-150 and SRPK1 separately and cooperatively participate into inflammatory responses in ALI through regulating AKT3 pathway. Increased miR-150 and silenced SRPK1 may be a novel potential factor for preventing and treating more inflammatory lung diseases.

In this study, we aim to investigate the role of miR-30a-5p in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) using LPS-induced A549 cells and mice. We found cell viability was significantly declined accompanied by cell apoptosis and cell cycle arrest at G0/G1 phase in LPS-treated A549 cells. MiR-30a-5p was down-regulated by LPS treatment and miR-30a-5p significantly protected A549 cells from LPS-induced injury by increasing cell viability, reducing cell apoptosis, promoting cell cycle progression, and inhibiting inflammatory reactions. Dual-luciferase activity demonstrated that RUNX2 was a direct target for miR-30a-5p and its expression was negatively and directly regulated by miR-30a-5p. Over-expression of RUNX2 weakened the inhibitory effect of miR-30a-5p on inflammatory injury. In vivo , over-expression of miR-30a-5p alleviated LPS-induced inflammatory responses and lung injury in LPS-administrated mice. Besides, miR-30a-5p repressed LPS-elevated phosphorylation levels of the signal transducer and activator of transcription 3 (STAT3) and c-Jun N-terminal kinase (JNK), IκBα degradation, and NF-κB p65 phosphorylation. In conclusion, miR-30a-5p ameliorates LPS-induced inflammatory injury in A549 cells and mice via targeting RUNX2 and related signaling pathways, thereby influencing the progression of ARDS.

The aberrant expression of microRNAs (miRNAs) is associated with the pathogenesis of inflammation-related diseases. However, the biological functions of miR-21 in acute lung injury (ALI) remain largely unknown. In this study, the level of miR-21 was obviously increased, but B cell lymphoma-2 (Bcl-2) expression was markedly decreased in LPS-treated human pulmonary alveolar epithelial cells (HPAEpiC). Suppression of miR-21 attenuated LPS-induced apoptosis and inflammation in HPAEpiC and promoted the survival of mice with ALI by decreasing the inflammatory cell count, release of cytokines and permeability in lung tissues. Importantly, Bcl-2 was a direct target of miR-21, and its expression was significantly inhibited by miR-21 mimics at a post-transcriptional level. Besides, Bcl-2 over-expression reversed miR-21-induced apoptosis and inflammation status and showed synergic effects with miR-21 inhibitor in LPS-treated HPAEpiC. In conclusion, inhibition of miR-21 could ameliorate apoptosis and inflammation by restoring the expression of Bcl-2 in LPS-induced HPAEpiC and mice, which might provide therapeutic strategies for the treatment of ALI.

MicroRNAs (miRNAs) play a vital role in regulating tumor progression. Dysregulated miR-136 expression was linked to the development of various human cancers. In the present study, we investigated the expression and relationship of miR-136 and COX2 in hepatocellular carcinoma (HCC) using relevant experiments, involving CCK-8, Transwell assay, and luciferase reporter assay. We demonstrated that miR-136 expression is obviously decreased in HCC tissues and cells, and negatively correlated with the expression of COX2 mRNA. In vitro assay revealed that overexpression of miR-136 significantly changed the expression of proliferation- and metastasis-related proteins and inhibited the proliferation, migration, and invasion of HepG2 and Hep3B cells. Dual-luciferase reporter assay validated that the 3'-untranslated region (3'-UTR) of COX2 is a direct target of miR-136. Furthermore, COX2 siRNA partially enhanced the miR-136 overexpression-induced inhibitory effects. In conclusion, miR-136 was vital in the regulation of HCC cell proliferation and metastasis by targeting COX2. Thus, our findings provided novel evidence that miR-136 might be recommended as a potential target for the diagnosis and treatment of HCC patients. [ABSTRACT FROM AUTHOR]