Microbiota and metabolite alterations in pancreatic head and body/tail cancer patients.

Pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) have distinct clinical and biological behaviors. The microbial and metabolic differences in PHC and PBTC have not been studied. The pancreatic microbiota and metabolome of 15 PHC and 8 PBTC tissues and their matched nontumor tissues were characterized using 16S rRNA amplicon sequencing and untargeted metabolomics. At the genus level, Bradyrhizobium was increased while Corynebacterium and Ruminococcus were decreased in the PHC tissues (Head T) compared with the matched nontumor tissues (Head N) significantly. Shuttleworthia, Bacillus, and Bifidobacterium were significantly decreased in the PBTC tissues (Body/Tail T) compared with the matched nontumor tissues (Body/Tail N). Significantly, Ileibacterium was increased whereas Pseudoxanthomonas was decreased in Head T and Body/Tail T, and Lactobacillus was increased in Head T but decreased in Body/Tail T. A total of 102 discriminative metabolites were identified between Head T and Head N, which were scattered through linoleic acid metabolism and purine metabolism pathways. However, there were only four discriminative metabolites between Body/Tail T and Body/Tail N, which were related to glycerophospholipid metabolism and autophagy pathways. The differential metabolites in PHC and PBTC were commonly enriched in alpha-linolenic acid metabolism and choline metabolism in cancer pathways. Eubacterium decreased in Head T was positively correlated with decreased linoleic acid while negatively correlated with increased arachidyl carnitine and stearoylcarnitine. Bacillus decreased in Body/Tail T was negatively correlated with increased L-carnitine. These microbiota and metabolites deserve further investigations to reveal their roles in the pathogenesis of PHC and PBTC, providing clues for future treatments.

NIR C-Myc Pu22 G-quadruplex probe as a photosensitizer for bioimaging and antitumor study.

Despite the fact that C-Myc G-quadruplex in the oncogene promoter regions is one of the crucial targets of antitumor drugs, the selectivities and proliferation inhibitions of its probes towards tumor cells remain a big challenge. Until now, no effective C-Myc G-quadruplex probes have been reported as a photosensitizer to increase their antitumor activities. Here, the first NIR C-Myc G-quadruplex probe PDS-SQ has been designed, comprising a G-quadruplex binder PDS and a squaraine dye SQ as a photosensitizer. Conjugate PDS-SQ could selectively NIR image C-Myc Pu22 G-quadruplex in tumor cells, and show stronger antitumor activity in the irradiation by a chemo-photodynamic method than in the dark. The study provides a new way to develop the novel NIR C-Myc G-quadruplex probes with more potent antitumor activities.

Single aromatics sulfonamide substituted dibenzothiazole squaraines for tumor NIR imaging and efficient photodynamic therapy at low drug dose.

On the base of the zwiterionic dibenzothiazole squaraine SQ, five cationic aromatics sulfonamide substituted dibenzothiazole squaraines SQ-D1 âˆ¼ 5 have been designed and synthesized. Through the formation of the cationic compound, a higher rigid structure and the addition of the strong electron-withdrawing group (-CN), an ideal photosensitizer SQ-D2 has been gotten. In all the sulfonaminosquaraines, compound SQ-D2 exhibited the highest ROS generation efficacy and photostability. It also showed the highest photo-cytotoxicity (IC50 = 0.25 ± 0.08 µM), very low dark-cytotoxicity and the excellent cell uptake. In animal study, it not only showed the effective tumor retention and the easy removal from the body, but also exhibited the effective PDT efficacy at low drug dose (0.15 mg/kg) and the good biocompatibility. Furthermore, photosensitizer SQ-D2 as a single component exhibited greater potential than clinically approved photosensitizer m-THPC and some nanomaterials with photosensitizers in PDT therapy towards human breast cancer. This work provides a new perspective to develop the ideal photosensitizer of the squaraine dyes.

CSC-pincer versus pseudo-pincer complexes of palladium(II): a comparative study on complexation and catalytic activities of NHC complexes.

Three thioether bridged diimidazolium dibromides with different steric and electronic properties have been synthesized as precursors to carbene-based CSC pincer ligands. Palladation afforded CSC Pd(II) pincer complexes for bulky and electron rich ligand systems, whereas the least donating ligand led to the formation of a pseudo-pincer complex. All complexes have been fully characterized by multinuclei NMR spectroscopies, ESI mass spectrometry and X-ray diffraction analysis. The catalytic activities of pincer versus pseudo-pincer complexes have been compared in the intermolecular hydroamination of alkynes with anilines as well.