AMPK reduces macrophage endotoxin tolerance through inhibition of TGF-ß1 production and its signaling pathway.

Adenosine monophosphate-activated protein kinase (AMPK) is involved in suppression of the development of endotoxin tolerance, which is a driver of the immunosuppression induced by sepsis. However, the mechanism by which AMPK inhibits the development of endotoxin tolerance has not been clearly elucidated. Therefore, the present study was performed to investigate the mechanism by which the AMPK activator, metformin, inhibits the development of endotoxin tolerance. Lipopolysaccharide (LPS) increased the production of transforming growth factor (TGF)-ß1 in macrophages, which was inhibited by metformin and resveratrol. Knockdown of AMPKα1 inhibited the suppressive effect of metformin on LPS-induced TGF-ß1 production. TGF-ß neutralizing antibody and TGF-ß type I receptor inhibitor increased the production of TNF-α and IL-6 via LPS restimulation in tolerized macrophages. LPS increased Smad2 phosphorylation, but this was inhibited in cells treated with TGF-ß neutralizing antibody or metformin. Smad2 knockdown inhibited the development of endotoxin tolerance, as evidenced by increased TNF-α production in response to LPS restimulation in tolerized macrophages. TGF-ß1 expression was increased, and the levels of TNF-α and IL-6 production induced by LPS stimulation were decreased, in splenocytes of cecal ligation and puncture (CLP) model mice compared to sham-operated controls. However, metformin treatment suppressed the production of TGF-ß1, and enhanced the production of TNF-α and IL-6 induced by LPS stimulation in splenocytes of CLP mice. These results indicated that AMPK activation inhibits LPS-induced TGF-ß1 production and its signaling pathway, thus suppressing the development of endotoxin tolerance in macrophages.

A prospective randomized study of different height of operation table for tracheal intubation with videolaryngoscopy in ramped position.

BACKGROUND: Previous studies have reported that the ramped position provides a better laryngoscopic view, reduces tracheal intubation time, and increases the success rate of endotracheal intubation. However, the patient's head height changes while in the ramped position, which in turn changes the relative positions of the patient and intubator. Thus, making these changes may affect the efficiency of tracheal intubation; however, few studies have addressed this problem. This study analyzed intubation time and conditions during tracheal intubation using videolaryngoscope in the ramped position. METHODS: This prospective study included 144 patients who were scheduled to receive general anesthesia for surgeries involving orotracheal intubation. The participants were randomly allocated to either the nipple or umbilical group according to the table height. Mask ventilation was assessed using the Warters grading scale. Tracheal intubation was performed using a McGrath MAC laryngoscope. The total intubation time, laryngoscopy time, tube insertion time, and difficulty of intubation (IDS score) were measured. RESULTS: The umbilical group had a significantly shorter laryngoscopy time (10 ± 3 vs. 16 ± 4 s), tube insertion time (18 ± 4 vs. 24 ± 6 s), and total intubation time (28 ± 5 vs. 40 ± 7 s) compared to the nipple group. No significant difference in the difficulty of mask ventilation was observed between the two groups. The IDS score was higher in the nipple than umbilical group. CONCLUSION: The lower (umbilical) table level reduced the intubation time and difficulty of videolaryngoscopy compared to the higher (nipple) table level. TRIAL REGISTRATION: This study was registered at KCT0005987, 11/03/2021, Retrospectively registered.

Tumor homing indocyanine green encapsulated micelles for near infrared and photoacoustic imaging of tumors.

Photoacoustic imaging (PAI) is an emerging analytical modality that is under intense preclinical development for the early diagnosis of various medical conditions, including cancer. However, the lack of specific tumor targeting by various contrast agents used in PAI obstructs its clinical applications. In this study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 receptor and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI.