Glutamate is one of the major excitatory neurotransmitters of the CNS and is essential for numerous key neuronal functions. However, excess glutamate causes massive neuronal death and brain damage owing to excitotoxicity via the glutamate receptors. Metabotropic glutamate receptor 5 (mGluR5) is one of the glutamate receptors and represents a promising target for studying neuroprotective agents of potential application in neurodegenerative diseases. Pu-erh tea, a fermented tea, mainly produced in Yunnan province, China, has beneficial effects, including the accommodation of the CNS. In this study, pu-erh tea markedly decreased the transcription and translation of mGluR5 compared to those by black and green teas. Pu-erh tea also inhibited the expression of Homer, one of the synaptic scaffolding proteins binding to mGluR5. Pu-erh tea protected neural cells from necrosis via blocked Ca2+ influx and inhibited protein kinase C (PKC) activation induced by excess glutamate. Pu-erh tea relieved rat epilepsy induced by LiCl-pilocarpine in behavioural and physiological assays. Pu-erh tea also decreased the expression of mGluR5 in the hippocampus. These results show that the inhibition of mGluR5 plays a role in protecting neural cells from glutamate. The results also indicate that pu-erh tea contains biological compounds binding transcription factors and inhibiting the expression of mGluR5 and identify pu-erh tea as a novel natural neuroprotective agent.

Herein, chondroitin sulfate-functionalized polyamidoamine (CS-PAMAM) was employed as a carrier in miR-34a delivery, and the inhibition of cell proliferation and migration of pancreatic cancer was systematically evaluated, using human pancreatic carcinoma cell line MiaPaCa-2 as a model. Through confocal laser scanning microscopy, an efficient cellular uptake of CS-PAMAM/miR-34a nanoparticles has been demonstrated to be executed in a CD44-dependent manner. After the successful delivery of miR-34a, the cell proliferation could be obviously inhibited due to the activation of cell apoptosis and cell cycle arrest. Meanwhile, CS-PAMAM-mediated miR-34a delivery could realize the suppression of cell migration elucidated by wound healing and transwell migration assays. Thus, the derivative CS-PAMAM could potentially be used as an effective carrier for miR-34a delivery to achieve the tumor gene therapy.

A hybrid gene carrier, HGP, has been successfully constructed through the genipin-mediated cross-linking of thermophilic histone and PEI25K. The thermophilic histone gene GK2215 was cloned from Geobacillus kastophilus HTA426 and overexpressed in Escherichia coli BL21. The thermophilic histone was systematically characterized and then cross-linked with PEI25K by genipin to obtain HGP. Notably, HGP exhibited superior transfection efficiency due to the synergistic effects between these two components: PEI25K mainly contributed to the condensation and transfer of pDNA, while thermophilic histone could enhance the endosomal escape and further nuclear location to achieve high gene expression. Meanwhile, HGP showed much lower cytotoxicity and hemolytic activity than PEI25K due to the introduction of nontoxic thermophilic histone. In addition, a strong intrinsic red fluorescence could be obviously observed in HGP. In conclusion, the protein–polymer hybrid carrier could potentially be used as a theranostic delivery system for achieving both efficient gene therapy and in vivo imaging.

A protein–polymer hybrid gene carrier HEP was successfully constructed based on thermophilic histone and polyethylenimine. The carrier exhibited low cytotoxicity and a high transfection efficiency due to the synergistic effects between the two components, which makes it a potential vehicle in tumor gene therapy.

•Porous PLGA microparticles harboring doxorubicin and PEI25K/p53 were prepared and characterized.•The microparticles exhibited an enhanced anticancer effect due to the synergistic cytotoxicity of doxorubicin and p53.•The microparticles provided a potential local drug delivery system by inhalation.In this study, porous PLGA microparticles for the co-delivery of doxorubicin and PEI25K/p53 were successfully prepared by the water–oil–water emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. The porous microparticles were obtained with a mean diameter of 22.9 ± 11.8 μm as determined by laser scattering particle size analysis. The particles’ surface porous morphology and distributions of doxorubicin and p53 were systematically characterized by scanning electron microscopy, flow cytometry, fluorescence microscopy and confocal laser scanning microscopy, revealing that doxorubicin and the plasmid were successfully co-encapsulated. Encapsulation efficiencies of 88.2 ± 1.7% and 36.5 ± 7.5% were achieved for doxorubicin and the plasmid, respectively, demonstrating that the porous structure did not adversely affect payload encapsulation. Microparticles harboring both doxorubicin and PEI25K/p53 exhibited enhanced tumor growth inhibition and apoptosis induction compared to those loaded with either agent alone in A549 human lung adenocarcinoma cells. Overall, the porous PLGA microparticles provide a promising anticancer delivery system for combined chemotherapy and gene therapy, and have great potential as a tool for sustained local drug delivery by inhalation.

A series of pyrrolo[1,2-a]pyrazinone compounds (5a–9f) were synthesized, and their cytotoxic activity against SKOV-3, A549, HeLa cells in vitro were evaluated by the MTT method. Some of the compounds showed potential antitumor activity against three tumor cell lines. Among them, compounds 9c and 9d showed the most potent cytotoxic activity. The preliminary mechanism of action was discussed.We synthesized a series of novel pyrrolo[1,2-a]pyrazinone compounds based on the pyrrolo[1,2-a]pyrazinone core of natural product Palau’amine using established synthetic methods to identify potential antitumor agents. Some of the compounds showed potent antitumor activity against SKOV-3, A549, HeLa tumor cell lines and the preliminary mechanism of action were discussed.

Metastasis and recurrence are the biggest obstacles to enhance the efficacy of surgical resection as a cure for hepatocellular carcinoma which is the second most deadly cancer in China. Here, we had showed that two DNAzymes (DRz1 and DRz2) targeted to IGF-II could inhibit invasion, motility and migration of SMMC-7721 cells in vitro. DRz1 was transfected into SMMC-7721 cells and the results were shown that IGF-II expression level dramatically reduced. Meanwhile, DRz1 effectively inhibited adhesion between SMMC-7721 cells with the extracellular matrix and Fb cells comparing to those untreated or transfected with inactive DRz (P < 0.05, ANOVA). Furthermore, vascular endothelial growth factor and matrix metalloproteinases were down-regulated in DRz1 treated cells. These results may help to identify novel therapeutic molecules targeting hepatocellular carcinomas.

In the past two decades, enzymatic polymerization has rapidly developed and become an important polymer synthesis technique. However, the range of polymers resulting from enzymatic polymerization could be further expanded through combination with chemical methods. This review systematically introduces recent developments in the combination of lipase-catalyzed polymerization with atom transfer radical polymerization (ATRP), kinetic resolution, reversible addition–fragmentation chain transfer (RAFT), click reaction and carbene chemistry to construct polymeric materials like block, brush, comb and graft copolymers, hyperbranched and chiral polymers. Moreover, it presents a thorough and descriptive evaluation of future trends and perspectives concerning chemoenzymatic polymerization. It is expected that combining enzymatic polymerization with multiple chemical methods will be an efficient tool for producing more highly advanced polymeric materials.

The tyrosine kinase, c-Abl, plays important roles in many aspects of cellular function. Previous reports showed that c-Abl is involved in NF-κB signaling. However, the functions of c-Abl in innate immunity are still unknown. Here we demonstrate that the mitochondrial antiviral signaling (MAVS) protein can be physically associated with c-Abl in vivo and in vitro. MAVS interacted with c-Abl through its Card and TM domain. A phosphotyrosine-specific antibody indicated that MAVS was phosphorylated by c-Abl. Functional impairment of c-Abl attenuated MAVS or VSV induced type-I IFN production. Importantly, c-Abl knockdown in MCF7 cells displayed impaired MAVS-mediated NF-κB and IRF3 activation. Taken together, our results suggest that c-Abl modulates innate immune response through MAVS.Structured summaryMINT-7297498, MINT-7297511, MINT-7297557, MINT-7297574: MAVS (uniprotkb:Q7Z434) physically interacts (MI:0915) with c-Abl (uniprotkb:P00519) by anti tag coimmunoprecipitation (MI:0007)MINT-7297542: c-Abl (uniprotkb:P00519) physically interacts (MI:0915) with MAVS (uniprotkb:Q7Z434) by anti bait coimmunoprecipitation (MI:0006)MINT-7297526: c-Abl (uniprotkb:P00519) physically interacts (MI:0915) with MAVS (uniprotkb:Q7Z434) by far western blotting (MI:0047)