University of South China

Glioblastoma is a life-threatening primary malignant brain tumor with an unfavorable prognosis. Contributing factors to its poor outcome include tumor heterogeneity, low mutational burden, and immunosuppression within the tumor microenvironment. Recognizing these challenges, immunotherapeutic strategies have emerged as a promising avenue for glioblastoma treatment. Although several dynamic research and scientific trend have increasingly taken pace in the immunotherapeutic approaches to glioblastoma, systematic bibliometric studies on such trends are few. On this note, this study explores a bibliometric analysis of the research hotspots and trends in glioblastoma immunotherapy. We conducted a search in the Web of Science Core Collection database for articles on glioblastoma immunotherapy published between 2004 and 2024. Using VOSviewer and CiteSpace software, we analyzed collected articles to explore aspects such as country of origin, journal of publication, affiliated institute, authorship, keywords, and citation patterns. As of May 1, 2024, we retrieved 3,729 papers on Glioblastoma Immunotherapy. In the field of glioblastoma immunotherapy, the United States stands out as the leading contributor, with 1,708 publications and a substantial 90,590 citations. Following closely, China has made significant contributions through 926 publications, earning 17,533 citations, while Germany adds to the body of knowledge with 349 publications and 16,355 citations. Furthermore, Authoritative journals in this field include Clinical Cancer Research and Neuro-Oncology. The top five keywords during this period were temozolomide, radiotherapy, dendritic cell, cytotoxic T lymphocyte, and vaccination. Moreover, Hotspots in the field include immune checkpoint inhibitors and chimeric antigen receptor T cell therapy.

The prognosis for severe asthma is poor, and the current treatment options are limited. The methyl-CpG binding domain protein 2 (MBD2) participates in neutrophil-mediated severe asthma through epigenetic regulation. Neutrophil extracellular traps (NETs) play a critical role in the pathogenesis of severe asthma. This study aims to detect if MBD2 can reduce NETs formation and the potential mechanism in severe asthma.

A severe asthma model was established in C57BL/6 wild-type mice exposure to house dust mite (HDM), ovalbumin (OVA), and lipopolysaccharide (LPS). Enzyme-linked immunosorbent assay was used to measure the concentrations of IL-4, IL-17A, and IFN-γ in lung tissues. Flow cytometry was employed to determine the percentages of Th2, Th17, and Treg cells in lung tissues. Quantitative real-time polymerase chain reaction was utilized to assess the mRNA expression levels of MBD2, JAK2, and PAD4. Western blotting and immunofluorescence were conducted to detect the protein of MBD2, JAK2, PAD4, and CitH3. HL-60 cells were differentiated into neutrophil-like cells by culturing in a medium containing dimethyl sulfoxide and then stimulated with LPS. KCC-07, Ruxolitinib, and Cl-amidine were used to inhibit the expressions of MBD2, JAK2, and PAD4, respectively.

Severe asthma mice were characterized by pulmonary neutrophilic inflammation and increased formation of neutrophil extracellular traps (NETs). The expression of MBD2, JAK2, and PAD4 was elevated in severe asthma mice. Inhibiting the expression of MBD2, JAK2, and PAD4 reduced NETs formation and decreased airway inflammation scores, total cell counts and neutrophil counts in BALF, and percentage of Th2 and Th17 cell in lung tissues, whereas increasing Treg cell counts. In both severe asthma mice and HL-60-differentiated neutrophil-like cells in vitro, inhibiting MBD2 reduced the mRNA and protein expression of JAK2 and PAD4, and inhibiting JAK2 reduced the expression of PAD4 mRNA and protein.

MBD2 regulates PAD4 expression through the JAK2 signaling pathway to promote NETs formation in mice with severe asthma. Further bench-based and bedside-based studies targeting the MBD2, PAD4, and JAK2 signaling pathways will help open new avenues for drug development of severe asthma.

Osteolysis is a common complication in patients with multiple myeloma (MM). Our previous studies have demonstrated that MM cells can promote osteoclast differentiation of macrophages. In this study, we explored the effect of sulforaphane (SFN), a natural NRF2 activator found in broccoli, on MM cell-induced osteoclast differentiation.

Conditional medium (CM) derived from MM cells was used to induce osteoclast differentiation, and TRAP staining was performed to examine osteoclast. Gene expression was detected by western blotting or real-time PCR. Cell counting and EdU staining were performed to test macrophage proliferation.

We showed that the CM of MM cells downregulated the expression of ferroportin1 (Fpn1), the only known iron exporter in vertebrate cells, thereby increasing cellular iron levels in murine macrophage cells RAW264.7. Deferoxamine (DFO), an iron chelator, effectively blocked MM cell CM-induced osteoclast differentiation and macrophage proliferation, suggesting that iron overload played a key role in these cellular events. Subsequent mechanistic investigations revealed that MM cell CM induced osteoclast differentiation and macrophage proliferation by activating the JNK/AP-1/NFATC1 pathway and PI3K/AKT pathway. SFN was found to increase Fpn1 expression, leading to decreased cellular iron levels in RAW264.7 cells activated by MM cell CM. Importantly, the osteoclast differentiation and macrophage proliferation induced by MM cell CM were significantly inhibited by SFN.

Altogether, our findings indicated that SFN inhibits MM cell-induced osteoclast differentiation and macrophage proliferation by elevating FPN1 levels. SFN could be a promising therapeutic strategy for MM-associated osteolysis.