Recent strategies for evoking immunogenic Pyroptosis in antitumor immunotherapy.

Pyroptosis is a specific type of programmed cell death (PCD) characterized by distinct morphological changes, including cell swelling, membrane blebbing, DNA fragmentation, and eventual cell lysis. Pyroptosis is closely associated with human-related diseases, such as inflammation and malignancies. Since the initial observation of pyroptosis in Shigella flexneri-infected macrophages more than 20 years ago, various pyroptosis-inducing agents, including ions, small molecules, and biological nanomaterials, have been developed for tumor treatment. Given that pyroptosis can activate the body's robust immune response against tumor and promote the formation of the body's long-term immune memory in tumor treatment, its status as a type of immunogenic cell death is self-evident. Therefore, pyroptosis should be used as a powerful anti-tumor strategy. However, there still is a lack of a comprehensive summary of the most recent advances in pyroptosis-based cancer therapy. Therefore, it is vital to fill this gap and inspire future drug design to better induce tumor cells to undergo pyroptosis to achieve advanced anti-tumor effects. In this review, we summarize in detail the most recent advances in triggering tumor cell immunogenic pyroptosis for adequate tumor clearance based on various treatment modalities, and highlight material design and therapeutic advantages. Besides, we also provide an outlook on the prospects of this emerging field in the next development.

Dual-Pronged Attack: pH-Driven Membrane-Anchored NIR Dual-Type Nano-Photosensitizer Excites Immunogenic Pyroptosis and Sequester Immune Checkpoint for Enhanced Prostate Cancer Photo-Immunotherapy.

Prostate cancer (PCa) is a frustrating immunogenic "cold" tumor and generally receives unsatisfied immunotherapy outcomes in the clinic. Pyroptosis is an excellent immunogenic cell death form that can effectively activate the antitumor immune response, promote cytotoxic T-lymphocyte infiltration, and convert tumors from "cold" to "hot." However, the in vivo application of pyroptosis drugs is seriously limited, and the upregulation of tumor PD-L1 caused by photo-immunotherapy further promotes immune escape. Herein, a new nano-photosensitizer (YBS-BMS NPs-RKC) with pH-response integrating immunogenic pyroptosis induction and immune checkpoint blockade is developed. The pH-responsive polymer equipped with the cell membrane anchoring peptide RKC is used as the carrier and further encapsulated with the near-infrared-activated semiconductor polymer photosensitizer YBS and a PD-1/PD-L1 complex small molecule inhibitor BMS-202. The pH-driven membrane-anchoring and pyroptosis activation of YBS-BMS NPs-RKC is clearly demonstrated. In vitro and in vivo studies have shown that this dual-pronged therapy stimulates a powerful antitumor immune response to suppress primary tumor progression and evokes long-term immune memory to inhibit tumor relapse and metastasis. This work provides an effective self-synergistic platform for PCa immunotherapy and a new idea for developing more biocompatible photo-controlled pyroptosis inducers.

Chuanxiong Formulae for Migraine: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials.

Objective: Migraine is a complex, prevalent and disabling neurological disorder characterized by recurrent episodes of headache without ideal treatment. We aim to assess the current available evidence of herbal Chuanxiong (Ligusticum chuanxiong Hort. root) formulae for the treatment of migraine according to the high-quality randomized controlled trials (RCTs). Methods: English and Chinese electronic databases were searched from their inceptions until March 2017. The methodological quality of included study was assessed by the Cochrane Collaboration risk of bias tool. RCTs with Cochrane risk of bias (RoB) score ≥4 were included in the analyses. Meta-analysis was conducted using RevMan 5.3 software. Publication bias was assessed by funnel plot analysis and Egger's test. Results: Nineteen RCTs with 1832 participants were identified. The studies investigated the Chuanxiong formulae vs. placebo (n = 5), Chuanxiong formulae vs. conventional pharmacotherapy (CP) (n = 13 with 15 comparisons), and Chuanxiong formulae plus CP vs. CP (n = 1). Meta-analysis indicated that Chuanxiong formulae could reduce frequency, duration, days and pain severity of migraine and improve the total clinical efficacy rate (P < 0.05). Adverse event monitoring was reported in 16 out of 19 studies and occurrence rate of adverse event was low. Conclusion: The findings of present study indicated that Chuanxiong formulae exerted the symptom reliefs of for migraine.