Recent studies have indicated that cancer stem-like cells (CSCs) exhibit a high resistance to current therapeutic strategies, including photodynamic therapy (PDT), leading to the recurrence and progression of colorectal cancer (CRC). In cancer, autophagy acts as both a tumor suppressor and a tumor promoter. However, the role of autophagy in the resistance of CSCs to PDT has not been reported. In this study, CSCs were isolated from colorectal cancer cells using PROM1/CD133 (prominin 1) expression, which is a surface marker commonly found on stem cells of various tissues. We demonstrated that PpIX-mediated PDT induced the formation of autophagosomes in PROM1/CD133+ cells, accompanied by the upregulation of autophagy-related proteins ATG3, ATG5, ATG7, and ATG12. The inhibition of PDT-induced autophagy by pharmacological inhibitors and silencing of the ATG5 gene substantially triggered apoptosis of PROM1/CD133+ cells and decreased the ability of colonosphere formation in vitro and tumorigenicity in vivo. In conclusion, our results revealed a protective role played by autophagy against PDT in CSCs and indicated that targeting autophagy could be used to elevate the PDT sensitivity of CSCs. These findings would aid in the development of novel therapeutic approaches for CSC treatment.

Severe acute respiratory syndrome (SARS) led to a life-threatening form of atypical pneumonia in late 2002. Following that, Middle East Respiratory Syndrome (MERS-CoV) has recently emerged, killing about 36% of patients infected globally, mainly in Saudi Arabia and South Korea. Based on a scaffold we reported for inhibiting neuraminidase (NA), we synthesized the analogues and identified compounds with low micromolar inhibitory activity against 3CL(pro) of SARS-CoV and MERS-CoV. Docking studies show that a carboxylate present at either R(1) or R(4) destabilizes the oxyanion hole in the 3CL(pro). Interestingly, 3f, 3g and 3m could inhibit both NA and 3CL(pro) and serve as a starting point to develop broad-spectrum antiviral agents.

Helicobacter pylori is well known as the primary cause of gastritis, duodenal ulcers, and gastric cancer. The pathogenic bacteria produces Lewis x and Lewis y epitopes in the O-antigens of lipopolysaccharides to mimic the carbohydrate antigens of gastric epithelial cells to avoid detection by the host's immune system. The enzyme alpha1,3-fucosyltransferase from H. pylori catalyzes the glycosyl addition of fucose from the donor GDP-fucose to the acceptor N-acetyllactosamine. The poor solubility of the enzyme was resolved by systematic deletion of the C-terminus. We report here the first structural analysis using CD spectroscopy and analytical ultracentrifugation. The results indicate that up to 80 residues, including the tail rich in hydrophobic and positively charged residues (sequence 434-478) and 5 of the 10 tandem repeats of 7 amino acids each (399-433), can be removed without significant change in structure and catalysis. Half of the heptad repeats are required to maintain both the secondary and native quaternary structures. Removal of more residues in the C-terminus led to major structural alteration, which was correlated with the loss of enzymatic activity. In accordance with the thermal denaturation studies, the results support the idea that a higher number of tandem repeats functioning to facilitate a dimeric structure helps to prevent the protein from unfolding during incubation at higher temperatures.