Multimodal Imaging-Guided Photoimmunotherapy of Pancreatic Cancer by Organosilica Nanomedicine.

Immune checkpoint blockade (ICB) treatments have contributed to substantial clinical progress. However, challenges persist, including inefficient drug delivery and penetration into deep tumor areas, inadequate response to ICB treatments, and potential risk of inflammation due to over-activation of immune cells and uncontrolled release of cytokines following immunotherapy. In response, this study, for the first time, presents a multimodal imaging-guided organosilica nanomedicine (DCCGP) for photoimmunotherapy of pancreatic cancer. The novel DCCGP nanoplatform integrates fluorescence, magnetic resonance, and real-time infrared photothermal imaging, thereby enhancing diagnostic precision and treatment efficacy for pancreatic cancer. In addition, the incorporated copper sulfide nanoparticles (CuS NPs) lead to improved tumor penetration and provide external regulation of immunotherapy via photothermal stimulation. The synergistic immunotherapy effect is realized through the photothermal behavior of CuS NPs, inducing immunogenic cell death and relieving the immunosuppressive tumor microenvironment. Coupling photothermal stimulation with αPD-L1-induced ICB, the platform amplifies the clearance efficiency of tumor cells, achieving an optimized synergistic photoimmunotherapy effect. This study offers a promising strategy for the clinical application of ICB-based combined immunotherapy and presents valuable insights for applications of organosilica in precise tumor immunotherapy and theranostics.

Integrated gut microbiota and metabolome analysis reveals the mechanism of Xiaoai Jiedu recipe in ameliorating colorectal cancer.

Introduction: Xiaoai Jiedu recipe (XJR), a classical prescription of traditional Chinese medicine (TCM), has been clinically proven to be effective in ameliorating colorectal cancer (CRC). However, its exact mechanism of action is still elusive, limiting its clinical application and promotion to a certain extent. This study aims to evaluate the effect of XJR on CRC and further illustrate mechanism underlying its action. Methods: We investigated the anti-tumor efficacy of XJR in vitro and vivo experiments. An integrated 16S rRNA gene sequencing and UPLC-MS based metabolomics approach were performed to explore possible mechanism of XJR anti-CRC on the gut microbiota and serum metabolic profiles. The correlation between altered gut microbiota and disturbed serum metabolites was investigated using Pearson's correlation analysis. Results: XJR effectively displayed anti-CRC effect both in vitro and in vivo. The abundance of aggressive bacteria such as Bacteroidetes, Bacteroides, and Prevotellaceae decreased, while the levels of beneficial bacteria increased (Firmicutes, Roseburia, and Actinobacteria). Metabolomics analysis identified 12 potential metabolic pathways and 50 serum metabolites with different abundances possibly affected by XJR. Correlation analysis showed that the relative abundance of aggressive bacteria was positively correlated with the levels of Arachidonic acid, Adrenic acid, 15(S)-HpETE, DL-Arginine, and Lysopc 18:2, which was different from the beneficial bacteria. Discussion: The regulation of gut microbiota and related metabolites may be potential breakthrough point to elucidate the mechanism of XJR in the treatment of the CRC. The strategy employed would provide theoretical basis for clinical application of TCM.

Biomimetic Gold Nanorods Modified with Erythrocyte Membranes for Imaging-Guided Photothermal/Gene Synergistic Therapy.

Pancreatic cancer (PC) is one of the most malignant cancers that develops rapidly and carries a poor prognosis. Synergistic cancer therapy strategy could enhance the clinical efficacy compared to either treatment alone. In this study, gold nanorods (AuNRs) were used as siRNA delivery vehicles to interfere with the oncogenes of KRAS. In addition, AuNRs were one of anisotropic nanomaterials that can absorb near-infrared (NIR) laser and achieve rapid photothermal therapy for malignant cancer cells. Modification of the erythrocyte membrane and antibody Plectin-1 occurred on the surface of the AuNRs, making them a promising target nanocarrier for enhancing antitumor effects. As a result, biomimetic nanoprobes presented advantages in biocompatibility, targeting capability, and drug-loading efficiency. Moreover, excellent antitumor effects have been achieved by synergistic photothermal/gene treatment. Therefore, our study would provide a general strategy to construct a multifunctional biomimetic theranostic multifunctional nanoplatform for preclinical studies of PC.

Wenzi Jiedu Recipe ameliorates colorectal cancer by remodeling the gut microbiota and tumor microenvironment.

Introduction: Wenzi Jiedu Recipe (WJR), traditional Chinese medicine (TCM) formula, has been proven to be clinically useful in the treatment of colorectal cancer (CRC). However, its underlying mechanisms are still elusive, which limits its wider application. Thus, we aimed to evaluate the effect of WJR on CRC and elucidate mechanisms underlying its action. Methods: Network pharmacology was employed to clarify the "herb-active ingredient-target" network of WJR. The 16S rDNA sequencing method was used to analyze the changes of gut microbes mediated by WJR in tumor-bearing mice with CRC. The proportions of CD4+ T cell and CD8+ T cell were measured by flow cytometry. Levels of the cytokines interleukin (IL)-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were assessed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Results: WJR showed significant anti-CRC effects both in vitro and in vivo. Network pharmacology revealed that WJR exerts anti-CRC therapeutic effect on multiple targets and signaling pathways. Gut microbiota analysis revealed that WJR therapy significantly enriched for Oscillibacter and Bacteroides_acidifacien. In particular, we found that WJR significantly increased the proportion of CD8+ T cells and the expression of immune-associated cytokines IL-10, IFN-γ, and TNF-α. Conclusion: The regulation of gut microbiota by WJR may be the breakthrough point to clarify its mechanism of action in the treatment of CRC, and it has a good prospect of clinical application.

The Relationship between Prevention and Treatment of Colorectal Cancer and Cancerous Toxin Pathogenesis Theory Basing on Gut Microbiota.

Gut microbiota is a diverse consortium of bacteria, fungi, protozoa, and viruses in the gut of all mammals. Gut microbiota remains in steady state under normal conditions. Changes in the internal and external environment may cause gut Microbiota to be out of tune. Malignant tumors are one of the major diseases currently endangering human health. CRC (colorectal cancer) has a significant upward trend in morbidity and mortality in many parts of the world. Technological advances have not yet brought about a breakthrough in the efficacy of CRC. The development of colon cancer is closely related to gut microbiota imbalance. According to more than 60 years of clinical practice, Professor Zhongying Zhou first proposed the pathogenesis theory of "cancerous toxin" in the 1990s and believed that cancerous toxin was a key pathogenesis of tumor development. Under the guidance of the theory of cancerous toxin, combined with clinical practice, Professor Zhou created an effective anticancer Chinese herbal compound, Jiedu Xiaoai Prescription. This paper summarizes recent hotspots related to gut microbiota and the occurrence, development, and prevention of colon cancer at home and abroad. The relationship between gut microbiota and cancerous toxin theory is proposed, and the feasibility of further studying the biological basis of cancerous toxin pathogenesis theory from the perspective of gut microbiota is pointed out.

A Survey on Perceptions of Complementary and Alternative Medicine among Undergraduates in China.

In recent years, complementary and alternative medicine (CAM) is more widely known and used globally. This study was the first to investigate undergraduates' attitude toward CAM, and influencing factors and barriers for students to use CAM. Students of five different grades in six universities of China were selected for this study from February to May 2019. First, the participants were divided into two groups based on their majors and fulfilled a previously validated 10-item CAM Health Belief Questionnaire (CHBQ) to evaluate their attitudes toward CAM. Second, the chi-square test was used to analyze the differences between the groups, and correlation analysis was conducted to investigate the relationship of the data between the two groups. Third, we used frequency analysis to identify the types that students wanted to study and the barriers to use CAM. The overall mean score of the CHBQ was 48.87 ± 8.594, which was higher than that in other countries. The students in lower grades had a stronger desire to learn CAM than those in higher grades (89% vs 83%, p < 0.05). "Too time-consuming and bad tastes," "Western medicine was enough," and "lack of relevant knowledge" were found to be the main interruptions for students to use CAM. 82.3% of students wanted CAM to be incorporated into the curriculum and desired to learn more about CAM. 72.3% of the students who had never learned CAM wanted to know more about CAM. 55.5% of the students were willing to recommend CAM. Most undergraduates desired to learn more about CAM. It is necessary to introduce or integrate CAM courses into the present curriculum, and it should be started in the lower grades. We hope this study can provide evidence for the authority in China to make appropriate changes and integrate CAM into the college curriculum.