Serum and glucocorticoid-regulated kinase 1 (SGK1) is a serine/threonine kinase belonging to the protein kinase A, G, and C (AGC) family. Upon initiation of the phosphoinositide 3-kinase (PI3K) signaling pathway, mammalian target of rapamycin complex 2 (mTORC2) and phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylate the hydrophobic motif and kinase domain of SGK1, respectively, inducing SGK1 activation. SGK1 modulates essential cellular processes such as proliferation, survival, and apoptosis. Hence, dysregulated SGK1 expression can result in multiple diseases, including hypertension, cancer, autoimmunity, and neurodegenerative disorders. This review provides a current understanding of SGK1, particularly in sodium transport, cancer progression, and autoimmunity. In addition, we summarize the developmental status of SGK1 inhibitors, their structures, and respective potencies evaluated in pre-clinical experimental settings. Collectively, this review highlights the significance of SGK1 and proposes SGK1 inhibitors as potential drugs for treatment of clinically relevant diseases.

Youngjun Park, Eui Man Jeong. IJSC 2024;17:270-83. https://doi.org/10.15283/ijsc24060

Here, we determined the immunostimulatory effects of black radish (Raphanus sativus ver niger) hot water extract (BRHE) on a mouse macrophage cell line (RAW 264.7) and mouse peritoneal macrophages. We found that BRHE treatment increased cell proliferation, phagocytic activity, nitric oxide (NO) levels, cytokine production, and reactive oxygen species synthesis. Moreover, BRHE increased the expression of the following immunomodulators in RAW 264.7 cells and peritoneal macrophages: pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), iNOS, and COX-2. BRHE treatment significantly up-regulated the phosphorylation of components of the mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), Akt, and STAT3 signaling pathways. Further, the effects of BRHE on macrophages were significantly diminished after the cells were treated with the TLR2 antagonist C29 or the TLR4 antagonist TAK-242. Therefore, BRHE-induced immunostimulatory phenotypes in mouse macrophages were reversed by multiple inhibitors, such as TLR antagonist, MAPK inhibitor, and Akt inhibitor indicating that BRHE induced macrophage activation through the TLR2/4–MAPK–NFκB–Akt–STAT3 signaling pathway. These results indicate that BRHE may serve as a potential immunomodulatory factor or functional food and provide the scientific basis for the comprehensive utilization and evaluation of black radish in future applications.

Cyclic peptides are one of the important chemical groups in the HDAC inhibitor family. Following the success of romidepsin in the clinic, naturally occurring cyclic peptides with a hydrophilic moiety have been intensively studied to test their function as HDAC inhibitors. Azumamides A-E, isolated from Mycale izuensis, are one of the powerful HDAC inhibitor classes. Structurally, azumamides A-E consist of three D-α-amino acids and unnatural β-amino acids such as 3-amino-2-methyl-5-nonenedioic acid-9-amide (Amnna) and 3-amino-2-methyl-5-nonenoic-1,9-diacid (Amnda). Moreover, azumamides have a retro-arrangement peptide backbone, unlike other naturally occurring cyclopeptide HDAC inhibitors, owing to the D-configuration of all residues. This review summarizes the currently available synthetic methods of azumamides A-E focusing on the synthesis of β-amino acids and macrocyclization. In addition, we overview the structure–activity relationship of azumamides A-E based on reported analogs. Collectively, this review highlights the potentiality of azumamides A-E as an HDAC inhibitor and provides further developmental insight into naturally occurring cyclic peptides in HDAC inhibition.

Kudoa septempunctata, a myxozoan, has been identified as the causative agent of foodborne illnesses associated with the consumption of raw olive flounder. To develop effective control methods against this parasite, fundamental research—including viability determination, transcriptome analysis, and antigenicity assessment of K. septempunctata myxospores—is required. This research necessitates the purification of the parasites. Sequential trypsin digestion, followed by density gradient purification, was performed to isolate the K. septempunctata myxospores. Further purification was achieved through fluorescence-activated cell sorting at a concentration of 106 to 107 myxospores/ml. The results demonstrated that the combination of trypsin digestion and density gradient methods consistently produced approximately 40 times more viable myxospores than the density gradient method alone. Additionally, the fluorescence-activated cell sorting method enhanced the purity of the myxospores by approximately 10%. The procedures described in this study will support research (such as RNA-sequencing, proteomics, vaccine antigen preparation) aimed at developing control methods for K. septempunctata including the fundamental research.