ß-Mangostin targets and suppresses glioma via STING activation and tumor-associated microglia polarization.

Glioma, a common and highly malignant central nervous system tumor, markedly influences patient prognosis via interactions with glioma-associated macrophages. Previous research has revealed the anticancer potential of ß-mangostin, a xanthone derivative obtained from the mangosteen fruit. This research investigated the role of ß-mangostin on microglia in the glioma microenvironment and evaluated the efficacy of ß-mangostin combined with anti-PD-1 antibody (αPD-1) in glioma-bearing mice. The results showed that, ß-mangostin attenuated M2 polarization in BV2 cells and promoted M1-related interleukin (IL)-1ß and IL-6 secretion, thereby inhibiting glioma invasion. In addition, ß-mangostin improved the anti-glioma effects of αPD-1 and increased CD8+T cell and M1-type microglia infiltration. Mechanistically, ß-mangostin bound to the stimulator of interferon genes (STING) protein, which is crucial for the anti-tumor innate immune response, and promoted STING phosphorylation in microglia, both in vivo and in vitro. These results provide insights into its mode of action and supporting further investigation into ß-mangostin as a therapeutic agent.

Self-Stimulated Photodynamic Nanoreactor in Combination with CXCR4 Antagonists for Antileukemia Therapy.

The treatment of acute myeloid leukemia (AML) remains unsatisfactory, owing to the absence of efficacious therapy regimens over decades. However, advances in molecular biology, including inhibiting the CXCR4/CXCL12 biological axis, have introduced novel therapeutic options for AML. Additionally, self-stimulated phototherapy can solve the poor light penetration from external sources, and it will overcome the limitation that traditional phototherapy cannot be applied to the treatment of AML. Herein, we designed and manufactured a self-stimulated photodynamic nanoreactor to enhance antileukemia efficacy and suppress leukemia recurrence and metastasis in AML mouse models. To fulfill our design, we utilized the CXCR4/CXCL12 biological axis and biomimetic cell membranes in conjunction with self-stimulated phototherapy. This nanoreactor possesses the capability to migrate into the bone marrow cavity, inhibit AML cells from infiltrating into the visceral organ, significantly enhance the antileukemia effect, and prolong the survival time of leukemic mice. Therefore, this nanoreactor has significant potential for achieving high success rates and low recurrence rates in leukemia treatment.

TRIM7 modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells.

OBJECTIVE: Glioblastoma is one of the most common intracranial malignant tumors with an unfavorable prognosis, and iron metabolism as well as ferroptosis are implicated in the pathogenesis of glioblastoma. The present study aims to decipher the role and mechanisms of tripartite motif-containing protein 7 (TRIM7) in ferroptosis and glioblastoma progression. METHODS: Stable TRIM7-deficient or overexpressing human glioblastoma cells were generated with lentiviral vectors, and cell survival, lipid peroxidation and iron metabolism were evaluated. Immunoprecipitation, protein degradation and ubiquitination assays were performed to demonstrate the regulation of TRIM7 on its candidate proteins. RESULTS: TRIM7 expression was elevated in human glioblastoma cells and tissues. TRIM7 silence suppressed growth and induced death, while TRIM7 overexpression facilitated growth and inhibited death of human glioblastoma cells. Meanwhile, TRIM7-silenced cells exhibited increased iron accumulation, lipid peroxidation and ferroptosis, which were significantly reduced by TRIM7 overexpression. Mechanistically, TRIM7 directly bound to and ubiquitinated nuclear receptor coactivator 4 (NCOA4) using K48-linked chains, thereby reducing NCOA4-mediated ferritinophagy and ferroptosis of human glioblastoma cells. Moreover, we found that TRIM7 deletion sensitized human glioblastoma cells to temozolomide therapy. CONCLUSION: We for the first time demonstrate that TRIM7 modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells, and our findings provide a novel insight into the progression and treatment for human glioblastoma.

MicroRNA-147a Targets SLC40A1 to Induce Ferroptosis in Human Glioblastoma.

Objective: Glioblastoma is one of the most common malignant tumors in the brain, and these glioblastoma patients have very poor prognosis. Ferroptosis is involved in the progression of various tumors, including the glioblastoma. This study aims to determine the involvement of microRNA (miR)-147a in regulating ferroptosis of glioblastoma in vitro. Methods: Human glioblastoma cell lines were transfected with the inhibitor, mimic and matched negative controls of miR-147a in the presence or absence of ferroptotic inducers. To knock down the endogenous solute carrier family 40 member 1 (SLC40A1), cells were transfected with the small interfering RNA against SLC40A1. In addition, cells with or without the miR-147a mimic treatment were also incubated with temozolomide (TMZ) to investigate whether miR-147a overexpression could sensitize human glioblastoma cells to TMZ chemotherapy in vitro. Results: We found that miR-147a level was decreased in human glioblastoma tissues and cell lines and that the miR-147a mimic significantly suppressed the growth of glioblastoma cells in vitro. In addition, miR-147a expression was elevated in human glioblastoma cells upon erastin or RSL3 stimulation. Treatment with the miR-147a mimic significantly induced ferroptosis of glioblastoma cells, and the ferroptotic inhibitors could block the miR-147a mimic-mediated tumor suppression in vitro. Conversely, the miR-147a inhibitor prevented erastin- or RSL3-induced ferroptosis and increased the viability of glioblastoma cells in vitro. Mechanistically, we determined that miR-147a directly bound to the 3'-untranslated region of SLC40A1 and inhibited SLC40A1-mediated iron export, thereby facilitating iron overload, lipid peroxidation, and ferroptosis. Furthermore, miR-147a mimic-treated human glioblastoma cells exhibited higher sensitivity to TMZ chemotherapy than those treated with the mimic control in vitro. Conclusion: We for the first time determine that miR-147a targets SLC40A1 to induce ferroptosis in human glioblastoma in vitro.

C21 Fraction Refined from Marsdenia tenacissima-Induced Apoptosis is Enhanced by Suppression of Autophagy in Human Gastric Cell Lines.

C21 steroidal glycosides have been extensively reported for treating several types of cancer and are widely found in Marsdenia tenacissima. In this study, a C21 fraction was synthesized from M. tenacissima, and its anti-cancer potency was assessed against in vitro gastric cell lines BGC-823, SGC-7901, and AGS. Significant growth inhibition and cell cycle arrest were observed in C21 fraction-treated gastric cancer cells. The results of apoptotic staining techniques in C21 fraction-treated gastric cells were confirmed with excess reactive oxygen species generation. Moreover, SOD and H2O2 levels were increased by C21 fraction, especially when combined with chloroquine (CQ). The apoptotic inducing potential of C21 fraction was also evidenced by upregulation of proapoptotic proteins cleaved-PARP and BAX and downregulation of antiapoptotic proteins Bcl-2 and p-AKT by western blot, especially in the presence of the autophagy inhibitor CQ. The results showed that the apoptosis of gastric cancer cells caused by C21 fraction was enhanced by inhibiting autophagy. The current findings reveal a new mechanism for the antitumor activity of C21 fraction on gastric cancer.

Risk factors and drug resistance in early-onset neonatal group B streptococcal disease.

In recent years, group B streptococcus (GBS) has become an important pathogen that causes infections in many neonatal organs, including the brain, lung, and eye (Ballard et al., 2016). A series of studies performed on GBS infections in western countries have revealed that GBS is one of the primary pathogens implicated in perinatal infection, and GBS infections are a major cause of neonatal morbidity and mortality in the United States (Decheva et al., 2013). In China, GBS is mainly found by screens for adult urogenital tract and perinatal infections, and neonatal GBS infections have been rarely reported. The incidence rate of early-onset neonatal GBS disease is thought to be lower in China than in western countries; however, this data is controversial since it also reflects the clinical interest in GBS (Dabrowska-Szponar and Galinski, 2001).