Genistein Induces Antiproliferative Activity and Apoptosis in Human Osteosarcoma Saos-2 Cells.

BACKGROUND/AIM: Genistein (4', 5, 7-trihydroxyisoflavone) and daidzein (4', 7-dihydroxyisoflavone) are isoflavones derived from soybean and have anti-cancer effects in various cells. However, the effects of genistein and daidzein on the human osteosarcoma cell line Saos-2 has not been investigated before. MATERIALS AND METHODS: Human osteosarcoma Saos-2 cells were treated with genistein for 24 and 48 hours. Cytotoxicity and apoptosis were measured. RESULTS: Genistein significantly inhibited proliferation of Saos-2 cells stronger than daidzein in a dose-dependent manner (0 to 80 µM). Genistein also significantly suppressed Saos-2 cell viability in a dose-dependent manner (0 to 100 µM). In contrast, daidzein did not affect Saos-2 cell viability. Real-time PCR revealed that genistein caused G1-arrest by increasing the expression of p21 and p27 mRNAs in Saos-2 cells. In addition, genistein induced apoptosis through the up-regulation of effector caspase-3/7 activity in Saos-2 cells. Genistein also enhanced initiator caspase-9 and TNF-α mRNA expression in cells. CONCLUSION: Genistein may inhibit proliferation through the up-regulation of p21 and p27 and viability by inducing apoptosis in Saos-2 cells.

Urosepsis Risk in Neuromyelitis Optica Spectrum Disorder Patients Administered Satralizumab.

Objective The interleukin-6 (IL-6) inhibitor satralizumab is an established treatment for neuromyelitis optica spectrum disorder (NMOSD). Although IL-6 inhibitors are generally well-tolerated, serious infections, including sepsis, can occur. In this study, we compared the sepsis characteristics in NMOSD patients administered satralizumab (NMOSD-satralizumab) to those in rheumatoid arthritis patients administered tocilizumab (RA-tocilizumab), another IL-6 inhibitor. Methods We examined adverse event reports from the Japanese Pharmaceuticals and Medical Devices Agency regarding NMOSD-satralizumab from August 2020 to March 2022 and RA-tocilizumab from April 2008 to November 2019 (term 1) and to March 2022 (term 2). Results We identified 6 sepsis cases in NMOSD-satralizumab, of which 5 (83%) developed from urinary tract infections (UTIs). Although data were unavailable for two patients, three cases had urologic complications in addition to recognized risk factors for serious infections, such as an older age, corticosteroid use, obesity, diabetes mellitus and motor disability. Urosepsis was relatively infrequent in RA-tocilizumab (term 1: 24.2%, term 2: 20.1%). Conclusion Safe satralizumab use requires risk factor assessment to minimize the incidence of severe infections. Management of UTIs is also recommended.

miR-34a-5p might have an important role for inducing apoptosis by down-regulation of SNAI1 in apigenin-treated lung cancer cells.

Apigenin is a flavonoid with antioxidant and anticancer effects. It has been reported that apigenin inhibits proliferation, migration, and invasion and induces apoptosis in cultured lung cancer cells. However, there is little information on the involvement of microRNAs (miRNAs) in its effects. miRNA microarray analysis and polymerase-chain-reaction analysis of miRNAs revealed that treatment of human lung cancer A549 cells with apigenin up-regulated the level of miR-34a-5p. Furthermore, mRNA microarray analysis and the results of three microRNA target prediction tools showed that Snail Family Transcriptional Repressor 1 (SNAI1), which inhibits the induction of apoptosis, had its mRNA expression down-regulated in A549 cells treated with apigenin. Our findings suggest that apigenin might induce apoptosis by down-regulation of SNAI1 through up-regulation of miR-34a-5p in A549 cells.

4-Hydroxyderricin inhibits osteoclast formation and accelerates osteoblast differentiation.

4-Hydroxyderricin (4-HD) is a major polyphenol of Angelica keiskei (Japanese name Ashitaba), exhibiting anti-allergic, anti-diabetic, anti-oxidant, and antitumor effects. The present study was designed to evaluate the effects of 4-HD on bone formation and maintenance by using cultured osteoclasts and osteoblasts. 4-HD did not affect cell proliferation of stromal ST2 cells and preosteoblast MC3T3-E1 cells at concentrations of 1-10 µM. This compound inhibited the formation of multinucleated osteoclasts from mouse splenic cells, and we identified a molecular pathway of osteoclast differentiation mediated by 4-HD, which led to inhibition of the expression of receptor activator of nuclear factor-κB ligand and macrophage-colony stimulating factor in ST2 cells. By contrast, 4-HD enhanced indices of osteoblast differentiation, such as alkaline phosphatase activity and calcium deposition by osteoblastic MC3T3-E1 cells, at concentrations of 1-10 µM. Furthermore, we found that 4-HD at 1 µM attenuated H2O2 levels in MC3T3-E1 cells. Our findings indicate that 4-HD may have critical effects on bone formation and maintenance.

A comparative proteomic analysis of the rat brain during rebound hyperphagia induced by space-restriction.

Although neurochemical changes have been reported in the brain in animal models of binge eating, biochemical changes of specific proteins in the brain are unknown. Our aim was to elucidate brain proteins altered in rats during enhanced rebound hyperphargia. Rats were deprived of food for 22 h/day for 6 days, then allowed free access to food for 24 h in normal cages (rebound hyperphargia) or in space-restricted cages (enhanced rebound hyperphargia). Proteins extracted from the rat brain were separated by two-dimensional gel electrophoresis, and compared with those from control rats freely fed for 7 days in normal cages. Proteins expressed differently from controls were identified by N-terminal amino acid sequencing and mass fingerprinting using a MALDI-TOF mass spectrometer. Among proteins in the corpus striatum, frontal lobe, hippocampus and thalamus/hypothalamus, ubiquitin C-terminal hydrolase L1 and peroxiredoxin 2 decreased in the hippocampus and phosphatidylethanolamine-binding protein increased in the thalamus/hypothalamus of rats with the enhanced rebound hyperphargia induced by space-restriction. In this study, we first demonstrated that three brain proteins changed in rats during enhanced rebound hyperphagia. These proteins might have pathophysiologic relevance to binge eating.