Ruyi Li

Bio: Ruyi Li is an academic researcher from Zhengzhou University. The author has contributed to research in topics: Tumor microenvironment & Angiogenesis. The author has co-authored 1 publications.

Natural Products: A Promising Therapeutics for Targeting Tumor Angiogenesis

Abstract: Tumor-associated angiogenesis is a key target for anti-cancer therapy. The imbalance between pro-angiogenic and anti-angiogenic signals elicited by tumor cells or tumor microenvironment always results in activating "angiogenic switch". Tumor angiogenesis functions in multi-aspects of tumor biology, including endothelial cell apoptosis, tumor metastasis, and cancer stem cell proliferation. Numerous studies have indicated the important roles of inexpensive and less toxic natural products in targeting tumor angiogenesis-associated cytokines and apoptotic signaling pathways. Our current knowledge of tumor angiogenesis is based mainly on experiments performed on cells and animals, so we summarized the well-established models for angiogenesis both in vitro and in vivo. In this review, we classified and summarized the anti-angiogenic natural agents (Polyphenols, Polysaccharides, Alkaloids, Terpenoids, Saponins) in targeting various tumor types according to their chemical structures at present, and discussed the mechanistic principles of these natural products on regulating angiogenesis-associated cytokines and apoptotic signaling pathways. This review is to help understanding the recent progress of natural product research for drug development on anti-tumor angiogenesis.

Platinum-Titania Schottky Junction as Nanosonosensitizer, Glucose Scavenger, and Tumor Microenvironment-Modulator for Promoted Cancer Treatment.

Abstract: To date, the construction of heterogeneous interfaces between sonosensitizers and other semiconductors or noble metals has aroused increasing attention, owing to an enhanced interface charge transfer, augmented spin-flip, and attenuated activation energy of oxygen. Here, a smart therapeutic nanoplatform is constructed by surface immobilization of glucose oxidase (GOx) onto a TiO2@Pt Schottky junction. The sonodynamic therapy (SDT) and starvation therapy (ST) mediated by TiO2@Pt/GOx (TPG) promote systemic tumor suppression upon hypoxia alleviation in tumor microenvironment. The band gap of TiO2@Pt is outstandingly decreased to 2.9 eV, in contrast to that of pristine TiO2. The energy structure optimization enables a more rapid generation of singlet oxygen (1O2) and hydroxyl radicals (•OH) by TiO2@Pt under ultrasound irradiation, resulting from an enhanced separation of hole-electron pair for redox utilization. The tumorous reactive oxygen species (ROS) accumulation and GOx-mediated glucose depletion facilitate oxidative damage and energy exhaustion of cancer cells, both of which can be tremendously amplified by Pt-catalyzed oxygen self-supply. Importantly, the combinatorial therapy triggers intense immunogenetic cell death, which favors a follow-up suppression of distant tumor and metastasis by evoking antitumor immunity. Collectively, this proof-of-concept paradigm provides an insightful strategy for highly efficient SDT/ST, which possesses good clinical potential for tackling cancer.

Endometriosis-Associated Angiogenesis and Anti-angiogenic Therapy for Endometriosis

Abstract: Endometriosis is a known estrogen-dependent inflammatory disease affecting reproductive-aged women. Common symptoms include pelvic pain, dysmenorrhea, dyspareunia, heavy menstrual bleeding, and infertility. The exact etiology of endometriosis is largely unknown, and, thus, the diagnosis and treatment of endometriosis are challenging. A complex interplay of many molecular mechanisms is thought to aid in the progression of endometriosis, most notably angiogenesis. This mini-review examines our current knowledge of the molecular etiology of endometriosis-associated angiogenesis and discusses anti-angiogenic therapy, in the blockade of endometriosis-associated angiogenesis, as potential non-hormonal therapy for the treatment of endometriosis.

Small Molecule Compounds of Natural Origin Target Cellular Receptors to Inhibit Cancer Development and Progression

Abstract: Receptors are macromolecules that transmit information regulating cell proliferation, differentiation, migration and apoptosis, play key roles in oncogenic processes and correlate with the prognoses of cancer patients. Thus, targeting receptors to constrain cancer development and progression has gained widespread interest. Small molecule compounds of natural origin have been widely used as drugs or adjuvant chemotherapeutic agents in cancer therapies due to their activities of selectively killing cancer cells, alleviating drug resistance and mitigating side effects. Meanwhile, many natural compounds, including those targeting receptors, are still under laboratory investigation for their anti-cancer activities and mechanisms. In this review, we classify the receptors by their structures and functions, illustrate the natural compounds targeting these receptors and discuss the mechanisms of their anti-cancer activities. We aim to provide primary knowledge of mechanistic regulation and clinical applications of cancer therapies through targeting deregulated receptors.

Saponins as cytotoxic agents: an update (2010–2021). Part II—Triterpene saponins

Abstract: Abstract Saponins make up an important group of natural glycosidic compounds which are distinguished by triterpene or steroidal aglycone. Although widely distributed in terrestrial flora, especially higher plants, they can also be found in some marine organisms. Cytotoxic activity is one of the most frequently reported from a wide array of pharmacological activities known for these metabolites. The current review is an update of our previous paper— Saponins as cytotoxic agents (Podolak et al. Phytochem Rev 9:425–474, 2010), and covers studies that were since published (2010–2021). This part refers to triterpene saponins and complements the first, which was devoted solely to steroidal saponins (Sobolewska et al. Phytochem Rev 19:139–189, 2020). Cytotoxic activities in vitro and in vivo are presented with a main focus on structure-activity relationships and molecular mechanisms of action.

Gastric Cancer-Derived Extracellular Vesicles (EVs) Promote Angiogenesis via Angiopoietin-2

Abstract: Simple Summary Angiogenesis is the formation of new blood vessels, which is essential for gastric cancer growth and metastasis. Angiopoietin-2 is a key driver of tumor angiogenesis and has recently emerged as a promising target for antiangiogenic therapy. Extracellular vesicles play an important role in tumor progression including angiogenesis. We explored the crosstalk between gastric cancer and endothelial cells mediated by vesicles, with a specific focus on angiopoietin-2. We show that primary gastric cancer and omental metastasis tissues express angiopoietin-2. We isolated gastric cancer vesicles and demonstrated that they induce the proliferation, migration, invasion, and tube formation of endothelial cells. Characterization of the angiogenic profile of these vesicles revealed high levels of proangiogenic proteins including angiopoietin-2. Using angiopoietin-2 knockdown, we demonstrate that angiopoietin-2 mediates the proangiogenic effects of the gastric cancer vesicles. Our findings suggest a new mechanism via which gastric cancer cells induce angiogenesis. Such a mechanism may be used as a target for cancer therapy. Abstract Angiogenesis is an important control point of gastric cancer (GC) progression and metastasis. Angiopoietin-2 (ANG2) is a key driver of tumor angiogenesis and metastasis, and it has been identified in primary GC tissues. Extracellular vesicles (EVs) play an important role in mediating intercellular communication through the transfer of proteins between cells. However, the expression of ANG2 in GC-EVs has never been reported. Here, we characterized the EV-mediated crosstalk between GC and endothelial cells (ECs), with particular focus on the role of ANG2. We first demonstrate that ANG2 is expressed in GC primary and metastatic tissues. We then isolated EVs from two different GC cell lines and showed that these EVs enhance EC proliferation, migration, invasion, and tube formation in vitro and in vivo. Using an angiogenesis protein array, we showed that GC-EVs contain high levels of proangiogenic proteins, including ANG2. Lastly, using Lenti viral ANG2-shRNA, we demonstrated that the proangiogenic effects of the GC-EVs were mediated by ANG2 through the activation of the PI3K/Akt signal transduction pathway. Our data suggest a new mechanism via which GC cells induce angiogenesis. This knowledge may be utilized to develop new therapies in gastric cancer.