Demethylzeylasteral is one of the extracts of Tripterygium wilfordii Hook F, which plays important roles in multiple biological processes such as inflammation inhibition, as well as immunosuppression. However, anti-cancer function and the underlying mechanisms of demethylzeylasteral in melanoma cells remain unclear. In this study, we demonstrate that demethylzeylasteral has an anti-tumor property in melanoma cells. Demethylzeylasteral not only inhibits cell proliferation through cell cycle arrest at S phase, but also induces cell apoptosis in melanoma cells. MCL1 is an anti-apoptotic protein in BCL2 family, and amplifies frequently in multiple human cancers. MCL1 is also known as a potential contributor for the resistance of BCL2 inhibitors, as well as various chemotherapeutic drugs. MCL1 is, therefore, regarded as a potential target for cancer therapy. Here, for the first time, we unveil that demethylzeylasteral suppresses the expression of MCL1. Interestingly, MCL1 interacts with S phase-related protein CDK2, and thereby inhibits it’s ubiquitin-dependent degradation. Together, demethylzeylasteral is a promising anti-tumor compound in melanoma cells. Demethylzeylasteral is also a potential inhibitor of MCL1.

A porphyrin-based electro-photodynamic imaging system was fabricated for monitoring the concentration of oxygen. Distinct from the electrochemiluminescent (ECL) inability of numerous organic species in aqueous solutions, a strong and stable red irradiation at 634 nm could be stimulated electrochemically on zinc(II) meso-tetra(4-carboxyphenyl) porphine (ZnTCPP)/tetraoctylammonium bromide (TOAB) in the physiological condition. In terms of in situ electron paramagnetic resonance and ECL spectroscopies, the nature of ECL was thoroughly investigated, being exactly the chemiluminescence from singlet oxygen (O) produced during the successive electro-reduction of ZnTCPP. Meanwhile, the excellent film-making capacity of amphiphilic TOAB as a potent ion barrier granted the luminophores a micro-order and patternable electrode modification. Such platform was exceptionally tolerant of pH variation, facilitating a durable solid-state ECL visualization under potentiostatic electrolysis and time exposure in the charge-coupled device (CCD) camera. For flow-injection and real-time detection, a chip-mounted microfluidic cell was customized and manufactured. A sensitive and simple vision-sensing of O was further achieved with a real determination limit as low as a few micromolar level. The developed ECL imaging system is a good prototype and an eco-friendly technique in the cathodic range, and thus, it would supplement the primary anodic imaging library, showing great promise for multiplexed and colorimetric assays as well as oxygen-involved activity studies in the future.

A Janus three-dimensional DNA nanomachine was constructed for the simultaneous and sensitive fluorescent detection and imaging of dual microRNAs in the cancer cells.

Dendritic cells (DCs) are a type of an antigen-presenting cell which undertake a job on capturing antigens coming from pathogens or tumors and presenting to T cells for immune response. The metabolism of DCs controls its development, polarization, and maturation processes and provides energy support for its functions. However, the immune activity of DCs in tumor microenvironment (TME) is inhibited generally. Abnormal metabolism of tumor cells causes metabolic changes in TME, such as hyperglycolysis, lactate and lipid accumulation, acidification, tryptophan deprivation, which limit the function of DCs and lead to the occurrence of tumor immune escape. Combined metabolic regulation with immunotherapy can strengthen the ability of antigen-presentation and T cell activation of DCs, improve the existing anti-tumor therapy, and overcome the defects of DC-related therapies in the current stage, which has great potential in oncology therapy. Therefore, we reviewed the glucose, lipid, and amino acid metabolism of DCs, as well as the metabolic changes after being affected by TME. Together with the potential metabolic targets of DCs, possible anti-tumor therapeutic pathways were summarized.

Early growth response protein 1 (EGR1), as a characteristic example of zinc finger proteins, acts as a transcription factor in eukaryotic cells, mediating protein-protein interactions. Here, a novel electrochemiluminescence (ECL)-based protocol for EGR1 assay was developed with a new eco-friendly emitter: singlet oxygen produced in the vicinity of nanoclay-supported zinc proto-porphyrin IX (ZnPPIX). Its electrochemical reduction stimulates an intense monochromic CL irradiation at 644 nm from the dissolved oxygen as endogenous coreactant in the aqueous solution. This ECL derivation was rationalized via hyphenated spectroscopy and theoretical calculation. To promote hydrophilicity and solid-state immobilization of porphyrins, the lamellar artificial laponite was employed as a nanocarrier owning to its large specific area without the blackbody effect. The facile exfoliation of laponite produced quality monolayered nanosheets and facilitated the adsorption and flattening of PPIX upon the surface, resulting in a highly efficient ECL emission. Based on the release of Zn(2+) in zinc finger domains of EGR1 upon contact with the ECL-inactive PPIX, which was monitored by circular dichroism and UV-absorption, a sensitive Zn(2+)-selective electrode for the "signal-on" detection of EGR1 was prepared with a detection limit down to 0.48 pg mL(-1) and a linearity over 6 orders of magnitude. The proposed porphyrin-based ECL system thus infused fresh blood into the traditional ECL family, showing great promise in bioassays of structural Zn(II) proteins and zinc finger-binding nucleotides.

Herein, a novel three-dimensional (3D) DNA nanomachine with high walking efficiency via free DNA walker movement on biomimetic lipid bilayers supported by hard silica@CdTe quantum dots (SiO 2 @CdTe) was constructed for ultrasensitive fluorescence detection of microRNA. The synthesized SiO 2 @CdTe nanoparticles were adopted as the fluorescence indicator and spherical carrier of lipid bilayers, and then the DNA substrates were anchored on lipid bilayers with biomimetic fluidity through the cholesterol-lipid interaction. Once target microRNA-141 interacted with the 3D DNA nanomachine to release cholesterol labeled arm (Cholarm), the Chol-arm could generate a series of strand displacement reactions by moving freely on the lipid bilayers, resulting in the releasement of numerous quenchers from the SiO 2 @CdTe nanoparticles and inducing a strong fluorescence signal. Impressively, compared with traditional 3D DNA nanomachine conjugating DNA substrates on hard surfaces (such as gold or silica) with limited reactivity, the proposed biomimetic 3D DNA nanomachine not only immobilized DNA substrates rapidly and effectively but also kept it with a favorable fluidity, which significantly enhanced the walking efficiency. As expected, the biomimetic 3D DNA nanomachine for fluorescence detection of microRNA-141 exhibited an excellent performance with a detection limit of 0.21 pM and presented promising properties in cell lysate detection and intracellular imaging. Thus, the described biomimetic 3D DNA nanomachine provided a novel avenue for sensitive detection of biomolecules, which could be useful for bioanalysis and early clinical diagnoses of disease.

Interleukin-17A (IL-17A), a proinflammatory cytokine mainly produced by T helper 17 cells, exerts protumor or antitumor effects in different cancer entities. However, the exact role of IL-17A in carcinogenesis and progression of tongue squamous cell carcinoma (TSCC) remains unclear. Here, we found that the levels of IL-17A in serum and tumor samples were significantly increased in TSCC patients and positively correlated with tumor metastasis and clinical stage. Besides, IL-17A enhanced cell migration and invasion in SCC15, a TSCC cell line. Furthermore, IL-17A inversely correlated with miR-23b expression in TSCC specimens. In vitro, NF-κB inhibited miR-23b transcription by directly binding to its promoter region. IL-17A downregulated miR-23b expression via activating NF-κB signaling pathway characterized by increasing p65 expression in the nuclear and elevating the levels of p-IKKα and p-IκBα. Overexpression of miR-23b inhibited, whereas knockdown of miR-23b promoted migration and invasion abilities of SCC15 cells. Moreover, extracellular matrix protein versican was proved to be the direct target of miR-23b through luciferase assay. IL-17A increased versican levels in vitro and knockdown of versican by siRNA inhibited SCC15 cell migration and invasion. Taken together, these results reveal a novel mechanism that IL-17A in TSCC microenvironment promotes the migration and invasion of TSCC cells through targeting miR-23b/versican pathway.

The prognostic value of platelet to lymphocyte ratio (PLR) in urologic cancer does not reach a consensus. Herein, we performed the meta-analysis to determine the prognostic role of PLR in patients with urologic cancer. A literature search was performed in the PubMed, Embase, and Web of Science databases. Hazard ratios (HRs) were extracted to estimate the association between PLR and prognosis. A total of 20 articles comprising 6079 patients were included in this study. The pooled results showed that a high PLR was significantly associated with worse prognosis of overall survival (OS) in urologic cancer [HR=1.65, 95% confidence interval (CI) =1.37-1.99, P<0.01]. The result also indicated that an elevated PLR was significantly associated with poor OS in renal cancer (HR=1.88, 95% CI=1.39-2.55, P<0.01). In addition, the significant association between poor OS and elevated PLR in renal cancer was consistent regardless of treatment, cut-off value, sample size and study quality. Our result also indicated that an elevated PLR predicted shorter OS (HR=1.78, 95% CI=1.38-2.30, P<0.01) and cancer-specific survival (HR=2.02, 95% CI=1.24-3.29, P<0.01) in prostate cancer. In conclusion, an elevated PLR was a predictive indicator of poor survival in renal cancer and prostate cancer.