Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Background: Infantile pneumonia is a respiratory infection disease, seriously threatening the life of neonatal patients. Circular RNA (circRNA) dysregulation is reported to be involved in pneumonia pathogenesis. Circ_0012535 was previously displayed to be upregulated in blood samples of patients with community-acquired pneumonia. ⋯ MiR-338-3p bound to IL6R 3'UTR, and circ_0012535 shared miR-338-3p binding site with IL6R. IL6R overexpression reversed the role of miR-338-3p, thereby recovering LPS-induced WI38 cell apoptosis and inflammation. Conclusion: Circ_0012535 supported LPS-induced WI38 cell apoptosis and inflammation to promote the progression of infantile pneumonia, and circ_0012535 functioned partly by targeting the miR-338-3p/IL6R signaling.
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Purpose: This study is designed to explore the role and mechanism of circ_0099188 in LPS-engendered HPAEpiC cells. Methods: Circ_0099188, microRNA-1236-3p (miR-1236-3p), and high mobility group box 3 (HMGB3) levels were measured using real-time quantitative polymerase chain reaction. Cell viability and apoptosis were assessed using cell counting kit-8 (CCK-8) and flow cytometry assays. ⋯ Also, the downregulation of circ_0099188 might overturn LPS-triggered HPAEpiC cell proliferation, apoptosis, and inflammatory response. Mechanically, circ_0099188 is able to affect HMGB3 expression by sponging miR-1236-3p. Conclusion: Circ_0099188 knockdown might mitigate LPS-induced HPAEpiC cell injury by targeting the miR-1236-3p/HMGB3 axis, providing an underlying therapeutic strategy for pneumonia treatment.
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Background: Immunosuppression caused by immune cell apoptosis and an imbalance of T helper 2 cells (T H 2) and T helper 1 cells (T H 1), is associated with poor outcomes in septic patients. Esmolol was reported to improve survival by modulating immune responses in septic shock. Whether esmolol could alleviate sepsis-induced immunosuppression and the optimal dose are unclear. ⋯ Conclusions: Low dose of esmolol reduced T-lymphocyte apoptosis and restored T H 2/T H 1 ratio in septic shock. Esmolol might modulate Akt/Bcl-2/Caspase-3 pathway to relieve T-lymphocyte apoptosis and inhibit Erk1/2 activity to decrease T H 0 differentiation to T H 2. Esmolol may be a potential immunoregulator of septic shock.
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Pulmonary epithelial barrier injury contributes to acute lung injury, accelerating exudate formation, and resulting alveolar edema. Heme oxygenase-1 (HO-1) plays an important role in ameliorating the pathological symptoms of acute lung injury (ALI). Using an ALI mouse model induced by LPS inhalation, the present study explored the potential molecular regulatory effect of hemin (a potent HO-1 inducer) against ALI epithelial damage. ⋯ Furthermore, HO-1 elevation inhibited the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome and oxidative stress in alveolar epithelia, leading to the suppression of inflammatory responses and epithelial pyroptosis, as indicated by the decreased levels of NLRP3 and apoptosis-associated speck-like protein containing a CARD domain (ASC), repressed cleavage of caspase-1 and gasdermin D, and reduced expression levels of inflammatory cytokine IL-1β. In contrast, protoporphyrin IX zinc (II) (ZnPP, an HO-1 inhibitor) treatment had no protective effect on LPS inhalation-induced ALI in mice. In summary, HO-1 induction serves a critical role in maintaining airway epithelium homeostasis through the inhibition of NLRP3/ASC/caspase-1-mediated pyroptosis and inflammation in the occurrence of ALI.
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Sepsis-induced cardiomyopathy (SIC) is one of the most common complications of infection-induced sepsis. An imbalance in inflammatory mediators is the main factor leading to SIC. N 6 -methyladenosine (m 6 A) is closely related to the occurrence and development of sepsis. ⋯ Serine protease inhibitor A3N-siRNA reduced LPS-induced inflammation of cardiac myocytes. In conclusion, the m 6 A reader YTHDC1 regulates SERPINA3N mRNA expression to mediate the levels of inflammation in SIC. Such findings add to the relationship between m 6 A reader YTHDC1 and SIC, providing a new research avenue for the therapeutic mechanism of SIC.