Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy.

As the first line of innate immune cells to migrate towards tumour tissue, neutrophils, can immediately kill abnormal cells and activate long-term specific adaptive immune responses. Therefore, the enzymes mediated elevation of reactive oxygen species (ROS) bioinspired by neutrophils can be a promising strategy in cancer immunotherapy. Here, we design a core-shell supramolecular hybrid nanogel via the surface phosphatase triggered self-assembly of oligopeptides around iron oxide nanoparticles to simulate productive neutrophil lysosomes. The cascade reaction of superoxide dismutase (SOD) and chloroperoxidase (CPO) within the bioinspired nanogel can convert ROS in tumour tissue to hypochlorous acid (HOCl) and the subsequent singlet oxygen (1O2) species. Studies on both cells and animals demonstrate successful 1O2-mediated cell/tumour proliferation inhibition, making this enzyme therapy capable for treating tumours without external energy activation.

Clinical Comparison of Spleen-Preserving Distal Pancreatectomy With or Without Splenic Vessel Preservation: A Systematic Review and Meta-Analysis.

OBJECTIVES: Spleen-preserving distal pancreatectomy with splenic vessel preservation (SVP) and only the save of short gastric and left gastroepiploic vessels called the Warshaw technique (WT) are the optimal procedures to resect benign or borderline malignant tumors of the left pancreas. The aim of this meta-analysis was to assess the intra- and postoperative outcomes between SVP and the WT. METHODS: We searched studies that compared the intra- and postoperative outcomes between SVP and the WT from PubMed, Embase, and the Cochrane Library (2004-2017). Dichotomous and continuous variables were calculated by the odds ratios and weighted mean differences with 95% confidence intervals. RESULTS: Eighteen retrospective studies, including 1039 patients, were eligible for our analysis. Six hundred seventy-nine patients (65.4%) underwent SVP, and 360 patients (34.6%) underwent the WT. Although the estimated blood loss in patients undergoing the WT was less than that in those undergoing SVP (P < .00001), SVP had a lower incidence of clinically relevant postoperative pancreatic fistula (P = .03), splenic infarcts (P < .00001), intra- and postoperative splenectomies (P = .0009), and gastric varices (P < .00001) than the WT. In addition, the tumor size of patients who underwent SVP was smaller (P = .006). CONCLUSIONS: Both SVP and the WT are feasible and effective surgical techniques. SVP should be given priority to reduce postoperative complications, and the WT should be regarded as a salvage operation to preserve the spleen based on the preoperative evaluation or in the case of uncontrolled bleeding during SVP.

Short-term in vitro culture of purity and highly functional rat bone marrow-derived mast cells.

Mast cells (MCs) are responsible for the innate immune response. Rat MCs are more suitable than mouse MCs as models of specific parasite infection processes and ovalbumin-induced asthma. Rat peritoneum-derived MCs and RBL-2H3 cells (an MC cell line) are widely used in disease studies. However, the application of rat bone marrow-derived MCs (BMMCs) are poorly documented in terms of the methodology of rat BMMC isolation. Here, we describe a relatively rapid, efficient, and simple method for the cultivation of rat BMMCs. As compared to previous protocols, rat BMMCs produced with the proposed protocol exhibited advantages in differentiation, proliferation, lifespan, and functionality, which should prove useful for studies of mucosal MC diseases in specific rat models.

Degranulation of gastrointestinal mast cells contributes to hepatic ischemia-reperfusion injury in mice.

The pathological changes following liver damage, including those caused by ischemia and reperfusion (I/R), are closely related to gastrointestinal dysregulation. Mast cells (MCs) are tissue-resident immune cells abundant in the gastrointestinal system that play diverse roles. In view of the characteristic localization of MCs around the microvasculature, we hypothesized that a stimulus-specific set of mediators released through degranulation of gastrointestinal MCs, which are enriched in hepatic sinusoids via the hepatic system, subsequently participate in associated pathological development within the liver. To elucidate the biological role of gastrointestinal MC granules in liver damage, we employed an experimental liver I/R model that allows conditional ablation of MCs. Marked degranulation was detected during I/R, which showed a significant positive correlation with liver damage. Our experiments further disclosed that MC degranulation primarily enhanced the cycle of inflammatory damage in I/R liver consisting of liver sinusoidal endothelial cell death, neutrophil infiltration, and formation of a neutrophil extracellular trap, with a concomitant increase in adhesion molecules, inflammatory cytokines, chemokines, and oxidative stress. Based on the collective results, we propose that suppression of activity or number of MCs may present an effective strategy for protection against hepatic I/R injury.

The development of methods for primary mast cells in vitro and ex vivo: An historical review.

Mast cells (MCs) are tissue-based stationary effector cells that form the immune system's first-line defense against various challenges. They are developed from the bone marrow-derived progenitors to complete their differentiation and maturation in the tissues where they eventually establish residence. MCs have been implicated in many diseases, such as allergy, parasitic infection, and neoplastic disorders. Immortalized MC lines, such as RBL-2H3, HMC-1, and LAD-2, are useful for investigating the biological functions of MC only to some extents due to the restriction of degranulation evaluation, in vivo injection and other factors. Over the past few decades, technologies for acquiring primarily MCs have been continually optimized, and novel protocols have been proposed. However, no relevant publications have analyzed and summarized these techniques. In this review, the classical approaches for extracting MCs are generalized, and new methods with potential values are introduced. We also evaluate the advantages and applicability of diverse MC models. Since MCs exhibit substantial plasticity and functional diversity due to different origins, it is both necessary and urgent to select a reliable and suitable source of MCs for a particular study.