Composite porphyrin-based conjugated microporous polymer/graphene oxide capable of photo-triggered combinational antibacterial therapy and wound healing.

Developing antibiotic-free treatment strategies to cope with the crisis on drug-resistant bacteria, are urgently needed. Antibiotics-independent physical approaches, especially the non-invasive phototherapies, worked through the assistance of photosensitizer (PS), have geared intensive attention and interests. Here, composite porphyrin-based conjugated microporous polymer/graphene oxide, denoted as GO-TAPP, combining the advantages of each component perfectly, was developed as broad-spectrum antibacterial agent. GO-TAPP, prepared via the self-oxidation coupling of tetraethynyl porphyrin on the surface of graphene oxide, could exert synergistic photothermal (PTT, ascribed to the graphene) and photodynamic (PDT, derived from the Porphyrin polymer) antimicrobial effectiveness. Both the in vivo and in vitro experiments have confirmed GO-TAPP are extremely potent against the Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) pathogens, which presents a remarkably enhanced sterilizing effect in comparison with its counterparts (the bare GO, and TAPP). Meanwhile, the synergistic effect of GO-TAPP could significantly accelerate the healing of open wound infected by bacterial. Altogether, this work proposed a new approach for the rational preparation of highly biocompatible graphene-based composite materials as antibiotic-free agents with synergistic antibacterial effect to combat bacterial infections.

A mitochondria-targeted far-red AIE fluorescent probe for distinguishing between mitophagy and ferroptosis in cancer cells.

A mitochondria-targeted far-red fluorescent probe LY-1 with AIE character was formulated to track cell viscosity alterations with excellent sensitivity and selectivity, which was used to discriminate between mitophagy and ferroptosis in cancer cells. Probe LY-1 is expected to be an effective vehicle for the diagnosis of mitochondrial viscosity relevant diseases.

Supramolecular Nanozyme System Based on Polydopamine and Polyoxometalate for Photothermal-Enhanced Multienzyme Cascade Catalytic Tumor Therapy.

The advent of enzyme-facilitated cascade events in which endogenous substrates within the human body are used to generate reactive oxygen species (ROS) has spawned novel cancer treatment possibilities. In this study, a supramolecular cascade catalytic nanozyme system was successfully developed, exhibiting photothermal-enhanced multienzyme cascade catalytic and glutathione (GSH) depletion activities and ultimately triggering the apoptosis-ferroptosis synergistic tumor therapy. The nanozyme system was fabricated using ß-cyclodextrin-functionalized polydopamine (PDA) as the substrate, which was then entangled with polyoxometalate (POM) via electrostatic forces and assembled with adamantane-grafted hyaluronic acid and glucose oxidase (GOx) via host-guest supramolecular interaction for tumor targeting and GOx loading. The catalytic function of GOx facilitates the conversion of glucose to H2O2 and gluconic acid. In turn, this process affirms the propitious generation of hydroxyl radical (•OH) through the POM-mediated cascade catalysis. Additionally, the POM species actively deplete the intracellular GSH pool, initiating a cascade catalytic tumor therapy. In addition, the PDA-POM-mediated photothermal hyperthermia boosted the cascade catalytic effect and increased ROS production. This confers considerable promise for photothermal therapy (PTT)/nanocatalytic cancer therapy on supramolecular nanozyme systems. The in vitro and in vivo antitumor efficacy studies demonstrated that the supramolecular cascade catalytic nanozyme system was effective at reducing tumor development while maintaining an acceptable level of biocompatibility. Henceforth, this study is to widen the scope of cascade catalytic nanoenzyme production using supramolecular techniques, as well as endeavor to delineate a prospective pathway for the application of PTT-enhanced nanocatalytic tumor therapy.

Synergistically enhanced cancer immunotherapy by combining protamine-based nanovaccine with PD-L1 gene silence nanoparticle.

Tumor vaccine has brought a new dawn for cancer immunotherapy, but disillusionary therapeutic outcomes have been achieved due to the inefficient in vivo vaccine delivery. Moreover, tumor cells customarily resort to various wily tricks to circumvent the recognition and sweeping of the immune system, the immune escape effect has badly aggravated the difficulty of cancer management. With respect to the foregoing, in this study, a promising combinational strategy which cooperated nanovaccine with immune escape inhibition was developed for synergistically enhancing the oncotherapy efficiency. On the one hand, natural polycationic macromolecule protamine (PRT) was utilized as the carrier to construct an antigen and adjuvant co-packaged nanovaccine for facilitating the ingestion in antigen-presenting cells, amplifying antigen cross-presentation and optimizing in vivo delivery. On the other hand, PD-L1 silence gene was selected and hitchhiked in a pH-responsive nanoparticle developed in our previous study. The therapeutic gene could be successfully delivered into the tumors to down-regulate PD-L1 expression and cripple tumor immune escape. The combination of nanovaccine with PD-L1 gene silence nanoparticle could synchronously stimulate antitumor immune responses and reduce immune escape, synergistically enhance the therapeutic efficiency. This study will furnish the prospective tactics for the research of cancer immunotherapy.

Characterization of methylthioadenosin phosphorylase (MTAP) expression in colorectal cancer.

PURPOSE: Tumour seriously affects people's quality of life. Colorectal cancer is a refractory tumour in digestive tract tumors. In colorectal cancer, gene expression abnormalities is the main reason for its incidence, we mainly focus on the molecular mechanism of MTAP in the development of colorectal cancer. METHODS: The tumour tissue and its adjacent tissue samples of 50 patients with colorectal cancer were screened from July 2011 to February 2015, and the expression of MTAP was detected. Cell lines that overexpress MTAP and low expression of MTAP were constructed in colorectal cancer cell lines. The cell proliferation, invasion and migration was detected in the cells with different expression levels of MTAP. Immunohistochemistry was used to detect the expression of MTAP in liver metastasis and to investigate its clinical significance. And statistics of clinical significance. RESULTS: Q-PCR results showed that the expression of MTAP in colorectal cancer cell lines were significantly higher than that normal human colonic myofibroblasts cell line. Cell proliferation test results showed that cell proliferation was accelerated when MTAP was overexpression, cell invasion and migration were simultaneously accelerated. The expression of MTAP in primary liver was positively correlated with metastatic disease in patients with liver metastatic colorectal cancer via EMT. CONCLUSIONS: MTAP accelerates the growth and metastasis of colorectal cancer through EMT.

Protective effects of trans-caryophyllene on maintaining osteoblast function.

Age-related osteoblast dysfunction is the main cause of age-related bone loss. Trans-caryophyllene (TC) is an important constituent of the essential oils derived from several species of medicinal plants. In this study, we investigated the effects of TC on osteoblast function in osteoblastic MC3T3-E1 cells. The results indicate that TC caused a significant elevation in collagen content, alkaline phosphatase activity, osteocalcin production, and mineralization, which are the four markers that account for the various stages of osteoblastic differentiation. In addition, pretreatment with TC prior to antimycin A exposure significantly reduced antimycin A-induced cell damage by attenuating cell death, preventing the release of reactive oxygen species and impeding osteoblast dysfunction. TC has been shown to be an agonist of the cannabinoid type 2 receptor (CB2R), and the effects of TC on osteocalcin secretion and matrix mineralization were abolished in MC3T3E1 cells transfected with CB2R siRNA. Our findings that TC promotes the formation of a mineralized extracellular matrix help to elucidate the role of CB2 signaling in the formation of bone and the maintenance of normal bone mass. © 2016 IUBMB Life, 69(1):22-29, 2017.

Activation of mTOR signaling leads to orthopedic surgery-induced cognitive decline in mice through ß-amyloid accumulation and tau phosphorylation.

Postoperative cognitive dysfunction (POCD) is a serious complication following surgery, however, the mechanism of POCD remains to be elucidated. Previous evidence has revealed that POCD may be associated with the pathogenesis of neurodegenerative processes. The mammalian target of rapamycin (mTOR) signaling pathway has been reported to be crucial in the pathophysiology of neurodegenerative diseases. However, the implications of mTOR in POCD remains to be fully elucidated. In the present study, western blotting and enzyme­linked immunosorbent assay were used to determine the expression of mTOR and any associated downstream targets; contextual fear conditioning was used to estimate the learning and memory ability of mice. Using an animal model of orthopedic surgery, it was found that surgical injury impaired hippocampal­dependent memory and enhanced the levels of phosphorylated mTOR at Serine­2448, phosphorylated 70­kDa ribosomal protein S6 kinase (p70S6K) at Threonine­389 with accumulation of ß­amyloid (Aß) and hyperphosphorylated tau at Serine-396, compared with the control group. Pretreatment with rapamycin, an mTOR inhibitor, restored the abnormal mTOR/p70S6K signaling induced by surgery, attenuated the accumulation of Aß and reduced the phosphorylation of tau protein. Rapamycin also reversed the surgery­induced cognitive dysfunction. The results of the present study suggested that the surgical stimulus activated mTOR/p70S6K signaling excessively, and that the inhibition of mTOR signaling with rapamycin may prevent postoperative cognitive deficits, partly through attenuating the accumulation of Aß and hyperphosphorylation of tau protein.