Pathogenic bacterial infections and drug resistance make it urgent to develop new antibacterial agents with targeted delivery. Here, a new targeting delivery nanosystem is designed based on the potential interaction between bacterial recognizing receptors on macrophage membranes and distinct pathogen‐associated molecular patterns in bacteria. Interestingly, the expression of recognizing receptors on macrophage membranes increases significantly when cultured with specific bacteria. Therefore, by coating pretreated macrophage membrane onto the surface of a gold–silver nanocage (GSNC), the nanosystem targets bacteria more efficiently. Previously, it has been shown that GSNC alone can serve as an effective antibacterial agent owing to its photothermal effect under near‐infrared (NIR) laser irradiation. Furthermore, the nanocage can be utilized as a delivery vehicle for antibacterial drugs since the gold–silver nanocage presents a hollow interior and porous wall structure. With significantly improved bacterial adherence, the Sa‐M‐GSNC nanosystem, developed within this study, is effectively delivered and retained at the infection site both via local or systemic injections; the system also shows greatly prolonged blood circulation time and excellent biocompatibility. The present work described here is the first to utilize bacterial pretreated macrophage membrane receptors in a nanosystem to achieve specific bacterial‐targeted delivery, and provides inspiration for future therapy based on this concept.
Platelet rich fibrin (PRF) has been utilized clinically as a platelet concentrate capable of stimulating tissue regeneration. Interestingly, several protocols have been proposed with little data obtained regarding the final cell counts following centrifugation. The aim of the present study was to compare different commercially available centrifuges and their respective protocols utilizing a novel method to quantify cells. One millimeter blood layers following centrifugation were sequentially pipetted from the upper layer downward until all 10 mL were harvested in sequential samples. Thereafter, each sample was sent for CBC analysis to accurately quantify precisely cell numbers within each separate blood layer following centrifugation. The results from this study revealed that L-PRF protocols (2700 rpm × 12 min) produced a clot with the majority of platelets and leukocytes concentrated within the buffy coat with relatively no cells found within the first 4 mL of L-PRF. Slower centrifugation protocols produced using the A-PRF protocols (1300 rpm × 8 min) produced a more evenly distributed number of platelets throughout PRF. Injectable-PRF (i-PRF) protocols produced the highest concentration of leukocytes/platelets, however, the total number of leukocytes and platelets were significantly lower owing to the decreased total volume collected. Horizontal centrifugation produced a significant increase in both the number and concentration of platelets and leukocytes (up to 3.5× higher for either solid/liquid PRF). When compared to either fixed or angled centrifuge (InstraSpin, Process for PRF). In conclusion, the present study revealed a novel/accurate method to quantify cells following PRF protocols. Furthermore, PRF produced via horizontal centrifugation accumulated a higher number and concentration of platelets/leukocytes when compared to either fixed-angle centrifugation. K E Y W O R D S blood platelets, centrifugation, fibrin, platelet rich fibrin
T cell immunotherapy holds significant challenges in solid tumors, mainly due to the T cells’ low activation and the decreased synthesis–release of therapeutic proteins, including perforin and granzyme B, which are present in lysosomes. In this study, a lysosome‐targeting nanoparticle (LYS‐NP) is developed by way of a mineralized metal–organic framework (MOF) coupled with a lysosome‐targeting aptamer (CD63‐aptamer) to enhance the antitumor effect of T cells. The MOF synthesized from Zn2+ and dimethylimidazole has good protein encapsulation and acid sensitivity, and is thus an ideal lysosomal delivery vector. Calcium carbonate (CaCO3) is used to induce MOF mineralization, improve the composite material's stability in encapsulating therapeutic protein, and provide calcium ions with synergistic effects. Before mineralization, perforin and granzyme B—T cell‐needed therapeutic proteins for tumors—are preloaded with the MOF. Moreover, T cells are pretreated with processed tumor‐specific antigens to activate or produce memory before reprogramming the lysosomes, facilitating the T cell receptor (TCR) for release of the therapeutic proteins. Using T cells recombined by LYS‐NPs, a significant enhancement of breast cancer control is confirmed.
Celastrol, also named as tripterine, is a pharmacologically active ingredient extracted from the root of traditional Chinese herb Tripterygium wilfordii Hook F with potent anti-inflammatory and anti-tumor activities. In the present study, we investigated the effects of celastrol on ulcerative colitis-related colorectal cancer (UC-CRC) as well as CRC in vivo and in vitro and explored its underlying mechanisms. UC-CRC model was induced in C57BL/6 mice by administration of azoxymethane (AOM) and dextran sodium sulfate (DSS). Colonic tumor xenograft models were developed in BALB/c-nu mice by subcutaneous injection with HCT116 and HT-29 cells. Intragastric administration of celastrol (2 mg/kg/d) for 14 weeks significantly increased the survival ratio and reduced the multiplicity of colonic neoplasms compared with AOM/DSS model mice. Mechanically, celastrol treatment significantly prevented AOM/DSS-induced up-regulation of expression levels of oncologic markers including mutated p53 and phospho-p53, β-catenin and proliferating cell nuclear antigen (PCNA). In addition, treatment with celastrol inhibited inflammatory responses, as indicated by the decrease of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, down-regulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and inactivation of nuclear factor κB (NF-κB). Moreover, celastrol obviously suppressed epithelial-mesenchymal transition (EMT) through up-regulating E-cadherin and down-regulating N-cadherin, Vimentin and Snail. Additionally, we also demonstrated that celastrol inhibited human CRC cell proliferation and attenuated colonic xenograft tumor growth via reversing EMT. Taken together, celastrol could effectively ameliorate UC-CRC by suppressing inflammatory responses and EMT, suggesting a potential drug candidate for UC-CRC therapy.
Helicobacter pylori infection occurs in more than half of the world’s population and is the main cause for gastric cancer. A series of lifestyle and nutritional factors, such as tobacco smoking and obesity, have been found to elevate the risk for cancer development. In this study, we sought to determine the immunological aspects during H. pylori infection and gastric cancer development. We found that B cells from H. pylori-infected patients presented altered composition and function compared to uninfected patients. IL-10-expressing CD24+CD38+ B cells were upregulated in H. pylori-infected patients, contained potent regulatory activity in inhibiting T cell pro-inflammatory cytokine secretion, and responded directly to H. pylori antigen stimulation. Interestingly, in H. pylori-infected smoking subjects and obese subjects, the number of IL-10+ B cells and CD24+CD38+ B cells were reduced compared to H. pylori-infected asymptomatic subjects. Regulatory functions mediated by CD24+CD38+ B cells were also impaired. In addition, gastric cancer positive patients had reduced IL-10-producing B cell frequencies after H. pylori-stimulation. Altogether, these data suggest that in H. pylori-infection, CD24+CD38+ B cell is upregulated and plays a role in suppressing pro-inflammatory responses, possibly through IL-10 production, a feature that was not observed in smoking and obese patients.
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