Leukocyte Telomeric G-Tail Length Shortening Is Associated with Esophageal Cancer Recurrence.

Despite significant advances in therapeutics for esophageal cancer (ESC) in the past decade, it remains the sixth most fatal malignancy, with a poor 5-year survival rate (approximately 10%). There is an urgent need to improve the timely diagnosis to aid the prediction of the therapeutic response and prognosis of patients with ESC. The telomeric G-tail plays an important role in the chromosome protection. However, aging and age-related diseases lead to its shortening. Therefore, the G-tail length has been proposed as a novel potential biomarker. In the present study, to examine the possibility of G-tail shortening in patients with ESC, we measured the leukocyte telomere length (LTL) and the G-tail length using a hybridization protection assay in 147 patients with ESC and 170 age-matched healthy controls. We found that the G-tail length in patients with ESC was shorter than that in the healthy controls (p = 0.02), while the LTL shortening was not correlated with the ESC incidence and recurrence. Our results suggest that the G-tail length reflects the physiological status of patients with ESC and is a promising biomarker for the diagnosis and prognosis of ESC.

N-doped carbon intercalated Fe-doped MoS2 nanosheets with widened interlayer spacing: An efficient peroxymonosulfate activator for high-salinity organic wastewater treatment.

Peroxymonosulfate (PMS) heterogeneous catalysis dominated by nonradical pathway showed excellent adaptability for pollutant removal in complex water matrixes. Herein, ultra-small Fe-doped MoS2 nanosheets with N-doped carbon intercalation (CF-MoS2) were synthesized via a one-step hydrothermal method to treat high salinity organic wastewater. CF-MoS2 exhibited an expanded interlayer spacing by 1.63 times and the specific surface area by 9 times compared with Fe-doped MoS2 (F-MoS2), substantially increasing the active sites. Homogeneous Fe2+ catalytic experiments confirmed that the promotion of carbon intercalated MoS2 (C-MoS2) on Fe3+/Fe2+ redox cycle was much higher than pure MoS2. Besides, the considerable removal of tetracycline (TC) under high salinity conditions (0-7.1%) was attributed to the dominant role of PMS nonradical oxidation pathways, including 1O2 and surface-bound radicals. The catalytic sites included Fe3+/Fe2+, Mo4+/Mo5+/Mo6+, C=O, pyridine N, pyrrolic N and hydroxyl groups. Finally, density functional theory (DFT) was employed to get the radical electrophilic attack sites and nucleophile attack sites of TC, and the results were consistent with the TC degradation products determined by HPLC-MS. This work would broaden the application of MoS2-based catalysts, especially for PMS catalytic removal of organic pollutants from high salinity wastewater.

Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1ß and IL-18 in the Septic Response.

Pyroptosis, an inflammatory form of programmed cell death, is the initiating event of sepsis and results in immune imbalance by releasing IL-1ß and IL-18 in the early stages. Studies show that enhancing autophagy via genetic manipulation can inhibit pyroptosis and prolong the survival of a sepsis animal model, indicating a possible therapeutic strategy against sepsis. However, almost no study so far has achieved pyroptosis inhibition via pharmacological autophagy induction in a sepsis disease model. To this end, we established an in vitro sepsis model by stimulating primary human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS), and analyzed the effect of the autophagy agonist rapamycin (RAPA) on pyroptosis. Phorbol 12-myristate 13-acetate- (PMA-) activated human THP-1 cells were used as the positive control. LPS significantly increased the levels of the pyroptotic protein Gasdermin D (GSDMD), cysteinyl aspartate-specific proteinase 1 (caspase-1), secreted LDH, IL-1ß, and IL-18. RAPA treatment downregulated the above factors and enhanced autophagy in the LPS-stimulated HUVECs and THP-1 cells. This study shows that RAPA abrogates LPS-mediated increase in IL-1ß and IL-18 by inhibiting pyroptosis and enhancing autophagy.

Recent Advances in Liquid Biopsy Based on Circulating Tumor DNA.

Many types of cells secrete DNA, RNA, and proteins through microvesicles, such as exosomes and apoptotic bodies, for the purpose of extracellular communication [...].

Umbilical Cord Blood Mesenchymal Stem Cells Enhance Lipopolysaccharide-Induced IL-10 and IL-37 Production in THP-1 Cells.

Umbilical cord blood mesenchymal stem cells (UCB-MSCs) have been shown to be a source of stem cells for use in cellular therapies and have immunomodulatory effects on several immune cells in an inflammatory environment. However, whether UCB-MSCs have immunomodulatory effects against lipopolysaccharide (LPS)-induced inflammatory cytokine secretion in macrophages and whether it is involved in phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway remain unclear. After co-culture of UCB-MSCs and phorbol 12-myristate 13-acetate (PMA)-activated human THP-1 cells using a transwell system, it showed that LPS significantly induced increases in the expression levels of interleukin 10 (IL-10), interleukin 37 (IL-37), phospho-PI3K (p-PI3K), and phospho-Akt (p-Akt) in macrophages. UCB-MSCs upregulated the expression of IL-10, IL-37, p-PI3K, and p-Akt, while it had no obvious effect on PI3K and Akt levels. Inhibitors of PI3K (LY294002) significantly suppressed the expression of IL-10, IL-37, p-PI3K, and p-Akt; however, it had no effect on the expression levels of PI3K and Akt. The present study demonstrated that UCB-MSCs increased the LPS-stimulated expression of IL-10 and IL-37 in macrophages through the PI3K/Akt signaling pathway.