Targeting PKM2 improves the gemcitabine sensitivity of intrahepatic cholangiocarcinoma cells via inhibiting ß-catenin signaling pathway.

Gemcitabine is considered the standard first-line chemotherapeutic agent for patients with intrahepatic cholangiocarcinoma (ICC). However, its therapeutic efficacy is hampered by the development of chemoresistance. Pyruvate kinase M2 (PKM2), a crucial mediator of the final step in glycolysis, has been implicated in the origination and advancement of diverse malignancies. Its expression is increased in many tumor types and this may correlate with increased drug sensitivity. However, the specific effect of PKM2 on the gemcitabine sensitivity in ICC remains to be elucidated. In this research, we aimed to elucidate the role and functional significance of PKM2 in ICC, as well as the heightened susceptibility of ICC cells to gemcitabine by targeting PKM2 and the underlying molecular mechanisms. Immunohistochemical and immunofluorescence analyses revealed elevated expression of PKM2 in both tumor cells and macrophages in human ICC tissues. Reducing PKM2 levels significantly restrained the proliferation of tumor cells, impeded cell cycle advance, induced programmed cell death, and suppressed metastasis. In addition, knockdown or pharmacological inhibition of PKM2 could enhance the response of ICC cells to gemcitabine in vitro. Interestingly, conditioned medium co-culture system suggested that conditioned medium from M2 macrophages increased gemcitabine sensitivity of ICC cells. However, silencing PKM2 or pharmacological inhibition of PKM2 in M2 macrophages did not ameliorate the gemcitabine resistance mediated by M2 macrophages derived conditioned medium. Mechanistically, downregulation of PKM2 repressed the expression of ß-catenin and its downstream transcriptional targets, thereby hindering the propagation of ß-catenin signaling cascade. Finally, the results of the subcutaneous xenograft experiment in nude mice provided compelling evidence of a synergistic interaction between PKM2-IN-1 and gemcitabine in vivo. In summary, we reported that PKM2 may function as an advantageous target for increasing the sensitivity of ICC to gemcitabine treatment. Targeting PKM2 improves the gemcitabine sensitivity of ICC cells via inhibiting ß-catenin signaling pathway.

One-step synthesis of functional metal organic framework composite for the highly efficient adsorption of tylosin from water.

Functional metal organic framework composite can effectively remove antibiotics from environmental water samples. However, designing excellent adsorbents with multiple active sites via a rapid one-step method is still a challenging problem. A novel metal organic framework composite (UiO-66-NH2-AMPS) was synthesized through one-step polymerization by adding functional monomer 2-acrylamide-2-methylpropanesulfonic acid (AMPS) during the preparation of UiO-66-NH2. The microstructure and morphology of the UiO-66-NH2-AMPS composite were characterized, and the adsorption performance towards tylosin (TYL) in water was explored by equilibrium adsorption experiment. The results illustrated that the adsorption equilibrium can be reached within 1 h, and the maximum binding amount of UiO-66-NH2-AMPS for TYL was 161.60 mg g-1, which was approximately 2.1-329 times of that of the other adsorbents. The pseudo second-order kinetic and Liu isotherm model were suitable for the adsorption process, and thermodynamic study displayed that the adsorption of UiO-66-NH2-AMPS composite for TYL is spontaneous and endothermal. The infrared and X-ray photoelectron spectra exhibited that hydrogen bond and electrostatic interaction were the primary recognition force for TYL. The UiO-66-NH2-AMPS composite have been successfully applied to remove TYL from environmental water. After 5 cycles, the removal efficiency of UiO-66-NH2-AMPS was still above 91.30%.

A new ionic liquid surface-imprinted polymer for selective solid-phase-extraction and determination of sulfonamides in environmental samples.

Toward improving the selective adsorption performance of molecularly imprinted polymers in strong polar solvents, in this work, a new ionic liquid functional monomer, 1-butyl-3-vinylimidazolium bromide, was used to synthesize sulfamethoxazole imprinted polymer in methanol. The resulting molecularly imprinted polymer was characterized by Fourier transform infrared spectra and scanning electron microscopy, and the rebinding mechanism of the molecularly imprinted polymer for sulfonamides was studied. A static equilibrium experiment revealed that the as-obtained molecularly imprinted polymer had higher molecular recognition for sulfonamides (e.g., sulfamethoxazole, sulfamonomethoxine, and sulfadiazine) in methanol; however, its adsorption of interferent (e.g., diphenylamine, metronidazole, 2,4-dichlorophenol, and m-dihydroxybenzene) was quite low. 1 H NMR spectroscopy indicated that the excellent recognition performance of the imprinted polymer was based primarily on hydrogen bond, electrostatic and π-π interactions. Furthermore, the molecularly imprinted polymer can be employed as a solid phase extraction sorbent to effectively extract sulfamethoxazole from a mixed solution. Combined with high-performance liquid chromatography analysis, a valid molecularly imprinted polymer-solid phase extraction protocol was established for extraction and detection of trace sulfamethoxazole in spiked soil and sediment samples, and with a recovery that ranged from 93-107%, and a relative standard deviation of lower than 9.7%.

Lactobacilli inhibit cervical cancer cell migration in vitro and reduce tumor burden in vivo through upregulation of E-cadherin.

The present study was designed to investigate the antitumor effects of Lactobacillus and the potential mechanisms. Cell Counting Kit-8 (CCK-8) assays were carried out to determine suitable doses for investigating the inhibitory effect of lactobacilli on cell migration ability of HeLa and U14 cells in vitro. In addition, western blot assays were performed to investigate the possible mechanisms corresponding to its antitumor effects. Furthermore, a xenograft mouse model was established for investigating the E-cadherin expression in tumor tissues after treatment with lactobacilli. Our results showed that live lactobacilli [multiplicity of infection (MOI) of 1,000:1] significantly possessed inhibitory effects on cell migration ability of cervical cancer cells. Lactobacilli (MOI: 1,000:1) significantly upregulated E-cadherin expressions in HeLa and U14 cells (p<0.05). On the contrary, our results showed that inactivated lactobacilli could not affect the E-cadherin expression levels in HeLa and U14 cells. Similar to the western blot assay, immunohistochemistry results also indicated that lactobacilli treatment significantly upregulated E-cadherin in tumor tissues (p<0.05). In conclusion, our results above suggest that lactobacilli have the potential for inhibiting the migratory ability of cervical cancer cell lines, and the possible pharmacological mechanism may be closely related to the upregulation of E-cadherin.