Inhibition of PI3K p110δ rebalanced Th17/Treg and reduced macrophages pyroptosis in LPS-induced sepsis.

Sepsis is a systemic inflammatory response syndrome caused by trauma or infection, which can lead to multiple organ dysfunction. In severe cases, sepsis can also progress to septic shock and even death. Effective treatments for sepsis are still under development. This study aimed to determine if targeting the PI3K/Akt signaling with CAL-101, a PI3K p110δ inhibitor, could alleviate lipopolysaccharide (LPS)-induced sepsis and contribute to immune tolerance. Our findings indicated that CAL-101 treatment improved survival rates and alleviated the progression of LPS-induced sepsis. Compared to antibiotics, CAL-101 not only restored the Th17/regulatory T cells (Treg) balance but also enhanced Treg cell function. Additionally, CAL-101 promoted type 2 macrophage (M2) polarization, inhibited TNF-α secretion, and increased IL-10 secretion. Moreover, CAL-101 treatment reduced pyroptosis in peritoneal macrophages by inhibiting caspase-1/gasdermin D (GSDMD) activation. This study provides a mechanistic basis for future clinical exploration of targeted therapeutics and immunomodulatory strategies in the treatment of sepsis.

Changes in Retinal Vessel Flow after Small Incision Lenticule Extraction.

Objective: In order to analyze changes in retinal vessel flow after small incision lenticule extraction (SMILE). Methods: A total of 32 patients (62 eyes) who underwent SMILE were enrolled in this prospective study. Optical parameters, including vessel density (VD), and perfusion density (PD) of foveal, parafoveal, and perifoveal regions, respectively, were measured before surgery and at 1 day, 1 week, 1 month, and 3 months postoperation. Preoperative parameters and surgical parameters were recorded. Results: Significant decreases in VD and PD on postoperative day 1 were detected in all quadrants, both in 3 mm and in 6 mm regions (P < 0.001). One month after surgery, VD returned to preoperative levels. None of the preoperative and surgical parameters were significantly correlated with the VD and PD fluctuations (all P > 0.05). Conclusion. VD may decrease significantly with regional disparity 1 day after SMILE while recovering at 1 month. Elevation of intraocular pressure due to suction may account for such changes.

MicroRNA-873 inhibits colorectal cancer metastasis by targeting ELK1 and STRN4.

MicroRNAs (miRNAs) are a group of small non-coding RNAs that directly bind to the 3'-untranslated-region (3'UTR) of mRNA, thereby blocking gene expression post-transcriptionally. Accumulating evidence prove that microRNA-873 (miR-873) functions as a promoter or suppressor in various cancers, while whether it affects the progression of colorectal cancer (CRC) is yet unknown. Here we found that miR-873 was downregulated in human CRC clinical samples, mouse CRC specimens and cell lines with high metastatic potential. We also demonstrated that low miR-873 expression was closely associated with poor prognosis of CRC. Overexpressing miR-873 suppressed proliferation and metastasis of CRC cells both in vitro and in vivo, while inhibiting miR-873 expression promoted the proliferation, migration and invasion in vitro. Moreover, miR-873 exerted its function by perturbing the ERK-CyclinD1 pathway and the epithelial-mesenchymal transition (EMT) process. Furthermore, we revealed that miR-873 acted as a tumor-suppressive microRNA by directly binding to the 3'UTRs of ELK1 and STRN4 and suppressed their expression. Our study uncovered an inhibitory role of miR-873 in CRC progression and might provide a promising marker for CRC diagnosis and prognosis.