Postoperative abdominal adhesion is one of the most common complications after abdominal surgery. A single drug or physical barrier treatment does not achieve the ideal anti-adhesion effect. We developed a thermosensitive hydrogel (PPH hydrogel) consisting of poloxamer 407 (P407), poloxamer (P188), and hydroxypropyl methylcellulose (HPMC) co-blended. An injectable thermosensitive TA/MMC-PPH hydrogel was obtained by loading tannic acid (TA) with an anti-inflammatory effect and mitomycin C (MMC), which inhibits fibroblast migration or proliferation. The optimal prescriptions of PPH hydrogels with a suitable gelling time (63 s) at 37 °C was 20% (w/v) P407, 18% (w/v) P188, and 0.5% (w/v) HPMC. The scanning electron microscopy (SEM) revealed that the PPH hydrogel had a three-dimensional mesh structure, which was favorable for drug encapsulation. The PPH hydrogel had a suitable gelation temperature of 33 °C, a high gel strength, and complicated viscosity at 37 °C, according to the rheological analysis. In vitro release studies have shown that the PPH hydrogel could delay the release of TA and MMC and conform to the first-order release rate. Anti-adhesion tests performed on rats in vivo revealed that TA/MMC-PPH hydrogel significantly reduced the risk of postoperative adhesion. In conclusion, the TA/MMC-PPH hydrogel prepared in this study showed an excellent performance in both controlled drug release and anti-adhesive effects. It can be used as a protocol to prevent or reduce postoperative abdominal adhesion.
Natural killer (NK) cells are the main effector of the innate immune response of cells undergoing a malignant transformation in cancer microenvironment. NK cells recognize their targets through a complex array of activating and inhibitory receptors, which regulate the intensity of the effector response against individual target cells. However, many studies have shown that the shortage of the major histocompatibility complex class I chain-related proteins A and B(MICA/B) on the surface of cancer cells can evade the recognition of immune cells and produce resistance to NK cell killing. Through consulting the database and molecular docking, it was found that pterostilbene (PTS;3,5-dimethoxy-40-hydroxystilbene) in blueberry extract may inhibit PI3K/AKT signaling pathway and up-regulate the expression of the MICA/B in cervical cancer. MTT assay, flow cytometry, colony formation assay and viability/cytotoxicity assay evaluated the effects of PTS on cervical cancer cell proliferation and apoptosis. The results of western blot and quantitative real-time polymerase chain reaction (qRT-PCR) further confirmed that PTS could regulate the cytolytic activity of NK cells to cancer cells by up-regulating the expression of MICA/B, and modulate the anti-cancer immune response in cervical cancer.
SLC16A1 and SLC16A3 (SLC16A1/3) are highly expressed in cervical cancers and associated with the malignant biological behavior of cancer. SLC16A1/3 is the critical hub for regulating the internal and external environment, glycolysis, and redox homeostasis in cervical cancer cells. Inhibiting SLC16A1/3 provides a new thought to eliminate cervical cancer effectively. There are few reports on effective treatment strategies to eliminate cervical cancer by simultaneously targeting SLC16A1/3. GEO database analysis and quantitative reverse transcription polymerase chain reaction experiment were used to confirm the high expression of SLC16A1/3. The potential inhibitor of SLC16A1/3 was screened from Siwu Decoction by using network pharmacology and molecular docking technology. The mRNA levels and protein levels of SLC16A1/3 in SiHa and HeLa cells treated by Embelin (EMB) were clarified, respectively. Furthermore, the Gallic acid-iron (GA-Fe) drug delivery system was used to improve its anti-cancer performance. Compared with normal cervical cells, SLC16A1/3 mRNA was over-expressed in SiHa and HeLa cells. Through the analysis of Siwu Decoction, a simultaneously targeted SLC16A1/3 inhibitor EMB was discovered. It was found for the first time that EMB promoted lactic acid accumulation and further induced redox dyshomeostasis and glycolysis disorder by simultaneously inhibiting SLC16A1/3. The gallic acid-iron-Embelin (GA-Fe@EMB) drug delivery system delivered EMB, which had a synergistic anti-cervical cancer effect. Under the irradiation of a near-infrared laser, the GA-Fe@EMB could elevate the temperature of the tumor area effectively. Subsequently, EMB was released and mediated the lactic acid accumulation and the GA-Fe nanoparticle synergistic Fenton reaction to promote ROS accumulation, thereby increasing the lethality of the nanoparticles on cervical cancer cells. GA-Fe@EMB can target cervical cancer marker SLC16A1/3 to regulate glycolysis and redox pathways, synergistically with photothermal therapy, which provides a new avenue for the synergistic treatment of malignant cervical cancer.
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