The development of necroptosis: what we can learn.

Necroptosis is a new type of programmed cell death discovered in recent years, playing an important role in various diseases. Since it was conceptualized in 2005, research on necroptosis has developed rapidly. However, few bibliometric analyses have provided a comprehensive overview of the field. This study aimed to employ a bibliometric analysis to assess necroptosis research's current status and hotspot, highlight landmark findings, and orientate future research. A total of 3993 publications from the WoSCC were collected for this study. Multiple tools were used for bibliometric analysis and data visualization, including an online website, VOSviewer, CiteSpace, and HistCite. Publications related to necroptosis have increased significantly annually, especially in the last 5 years. Globally, the USA and Harvard University are the most outstanding countries and institutions in this field, respectively. The academic groups managed by Peter Vandenabeele and Junying Yuan both have permanent and intensive research on necroptosis. Cell Death and Differentiation is the most vital journal in this field. The molecular mechanisms of necroptosis and its role in disease are the focus of current research, while the crosstalk between programmed cell death is an emerging direction in the field. The "reactive oxygen species", "innate immunity", and "programmed cell death" may be potential research hotspots. Our results present a comprehensive knowledge map and explore research trends. Researchers and funding agencies on necroptosis can obtain helpful references from our study.

Low-intensity pulsed ultrasound-generated singlet oxygen induces telomere damage leading to glioma stem cell awakening from quiescence.

Cancer stem cells, quiescent and drug resistant, have become a therapeutic target. Unlike high-intensity focused ultrasound directly killing tumor, low-intensity pulsed ultrasound (LIPUS), a new noninvasive physical device, promotes pluripotent stem cell differentiation and is primarily applied in tissue engineering but rarely in oncotherapy. We explored the effect and mechanism of LIPUS on glioma stem cell (GSC) expulsion from quiescence. Here, we observed that LIPUS led to attenuated expression of GSC biomarkers, promoted GSC escape from G0 quiescence, and significantly weakened the Wnt and Hh pathways. Of note, LIPUS transferred sonomechanical energy into cytochrome c and B5 proteins, which converted oxygen molecules into singlet oxygen, triggering telomere crisis. The in vivo and in vitro results confirmed that LIPUS enhanced the GSC sensitivity to temozolomide. These results demonstrated that LIPUS "waked up" GSCs to improve their sensitivity to chemotherapy, and importantly, we confirmed the direct targeted proteins of LIPUS in GSCs.

Retracted: Combined therapy using LHRH-PE40 and anti-CD40 dendritic cells substantially eliminate tumor cells.

LHRH-PE40 was used to promote the proliferation of bone marrow derived cell (BMDC) and improve the antigen-presenting ability of BMDC as well as the immune function via the CD40 signal pathway. LHRH-PE40 was also implicated in cancer treatment, targeting a variety of cancer cells that express luteinizing hormone-releasing hormone receptor (LHRHR). In the present study, the mechanism and efficacy of LHRH-PE40 were addressed in the following three aspects. Enzyme-linked immunosorbent assay was performed to confirm the binding specificity of LHRH-PE40 to LHRHR. The killing effect of LHRH-PE40 on target cells was mediated by LHRHR, which specifically killed LHRHR-positive target cells while the minimal cytotoxicity of LHRHR-negative cells is negligible. Spiegelmers, a molecule mutually exclusive with GnRH and developed by Sven Klussmann and Dr Sven Klussmann of NOXXON Pharmaceuticals in Germany, demonstrated that LHRH-PE40 maintains a combinatory characteristics of LHRH and LHRHR. In the end, the mechanism of LHRH-PE40 underlying induction of apoptosis at low concentration and prolonged conditions was firstly demonstrated by the basic method of detecting apoptosis to induce apoptosis. It provided a scientific basis for clinical application of LHRH-PE40 and laid a foundation for the further study of LHRH-PE40 on inducing apoptosis of target cells. The target cells herein refer to tumor cells that overexpress LHRHR. This study shows that activated DC can more effectively promote the proliferation of CD4+ T cells, and initially proved that DC carrying anti-CD40 antibody promoted the immune treatment of the tumor. Combining LHRH-PE40 with anti-CD40 DCs achieved substantially improved efficacy in killing tumor cells.

Optimizing the extraction of anti-tumor polysaccharides from the fruit of Capparis spionosa L. by response surface methodology.

Capparis spionosa L. is a traditional medicinal plant in China and central Asia. In this study, an experiment was designed to investigate the optimization of the extraction of anti-tumor polysaccharides from the fruit of Capparis spionosa L. (CSPS) by response surface methodology (RSM). Four independent variables (extraction temperature, extraction time, ratio of water to sample and extraction cycles) were explored. Meanwhile, the in vivo anti-tumor activity of CSPS was investigated. The results showed that the experimental data could be fitted to a second-order polynomial equation using multiple regression analysis. The optimum extraction conditions were as follows: extraction temperature 92 °C, extraction time 140 min, ratio of water to sample 26 mL/g, and three extraction cycle. Under these conditions, the yield of polysaccharides reached 13.01%, which was comparable to the predicted yield (12.94%, p > 0.05). This indicated that the model was adequate for the extraction process. Additionally, CSPS could prolong the survival time of H22 bearing mice in vivo. The anti-tumor activities of CSPS were dose-dependent.