Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway.

BACKGROUND: Recent studies suggested that NDUFS1 has an important role in human cancers; however, the effects of NDUFS1 on gastric cancer (GC) are still not fully understood. METHODS: We confirmed that NDUFS1 is downregulated in GC cells through western blot immunohistochemistry and bioinformation analysis. The effect of NDUFS1 on GC was studied by CCK-8, colony formation, transwell assay in vitro and Mouse xenograft assay in vivo. Expression and subcellular localization of NDUFS1 and the content of mitochondrial reactive oxygen species (mROS) was observed by confocal reflectance microscopy. RESULTS: Reduced expression of NDUFS1 was found in GC tissues and cell lines. Also, NDUFS1 overexpression inhibited GC cell proliferation, migration, and invasion in vitro as well as growth and metastasis in vivo. Mechanistically, NDUFS1 reduction led to the activation of the mROS-hypoxia-inducible factor 1α (HIF1α) signaling pathway. We further clarified that NDUFS1 reduction upregulated the expression of fibulin 5 (FBLN5), a transcriptional target of HIF1α, through activation of mROS-HIF1α signaling in GC cells. CONCLUSIONS: The results of this study indicate that NDUFS1 downregulation promotes GC progression by activating an mROS-HIF1α-FBLN5 signaling pathway.

Cancer-associated fibroblasts promote proliferation, angiogenesis, metastasis and immunosuppression in gastric cancer.

Despite advances in surgery, radiotherapy and immunotherapy, the mortality rate for gastric cancer remains one of the highest in the world. A large body of evidence has demonstrated that cancer-associated fibroblasts (CAFs), as core members of the stroma, can secrete cytokines, proteins and exosomes to create a tumour microenvironment that is conducive to cancer cell survival. CAFs can also interact with cancer cells to form a complex signalling network, enabling cancer cells to more easily metastasise to other organs and tissues in the body and develop metastatic foci. In this review, we provide an overview of the CAFs concept and activators. We focus on elucidating their effects on immune cells, intratumoural vasculature, extracellular matrix, as well as cancer cell activity, metastatic power and metabolism, and on enhancing the metastatic ability of cancer cells through activation of JAK/STAT, NF/κB and CXCL12/CXCR4. Various therapeutic agents targeting CAFs are also under development and are expected to improve the prognosis of gastric cancer in combination with existing treatment options.

ESM1 Interacts with c-Met to Promote Gastric Cancer Peritoneal Metastasis by Inducing Angiogenesis.

The peritoneum is the most common metastatic site of advanced gastric cancer and is associated with extremely poor prognosis. Endothelial-specific molecule 1 (ESM1) was found to be significantly associated with gastric cancer peritoneal metastasis (GCPM); however, the biological functions and molecular mechanisms of ESM1 in regulating GCPM remain unclear. Herein, we demonstrated that ESM1 expression was significantly upregulated in gastric cancer tissues and positively correlated with platelet endothelial cell adhesion molecule-1 (CD31) levels. Moreover, clinical validation, in in vitro and in vivo experiments, confirmed that ESM1 promoted gastric cancer angiogenesis, eventually promoting gastric cancer peritoneal metastasis. Mechanistically, ESM1 promoted tumor angiogenesis by binding to c-Met on the vascular endothelial cell membrane. In addition, our results confirmed that ESM1 upregulated VEGFA, HIF1α, and MMP9 expression and induced angiogenesis by activating the MAPK/ERK pathway. In conclusion, our findings identified the role of ESM1 in gastric cancer angiogenesis and GCPM, thus providing insights into the diagnosis and treatment of advanced gastric cancer.

CST1 inhibits ferroptosis and promotes gastric cancer metastasis by regulating GPX4 protein stability via OTUB1.

Metastasis is an important factor contributing to poor prognosis in patients with gastric cancer; yet, the molecular mechanism leading to this cell behavior is still not well understood. In this study, we explored the role of cysteine protease inhibitor SN (Cystatin SN, CST1) in promoting gastric cancer metastasis. We hypothesized that CST1 could regulate gastric cancer progression by regulating GPX4 and ferroptosis. Whole transcriptome sequencing suggested that the expression of CST1 was significantly increased in metastatic cancer, and high CST1 expression was correlated with a worse prognosis. Our data further confirmed that the overexpression of CST1 may significantly promote the migration and invasion of gastric cancer cells in vitro and enhance liver, lung, and peritoneal metastasis of gastric cancer in nude mice. Meanwhile, high expression of CST1 promoted the epithelial-mesenchymal transition (EMT) of gastric cancer cells. Mechanistically, a co-immunoprecipitation experiment combined with mass spectrometry analysis confirmed that CST1 could interact with GPX4, a key protein regulating ferroptosis. CST1 relieves GPX4 ubiquitination modification by recruiting OTUB1, improving GPX4 protein stability and reducing intracellular reactive oxygen species (ROS), thereby inhibiting ferroptosis and, in turn, promoting gastric cancer metastasis. Moreover, clinical data suggested that CST1 is significantly increased in peripheral blood and ascites of gastric cancer patients with metastasis; multivariate Cox regression model analysis showed that CST1 was an independent risk factor for the prognosis of gastric cancer patients. Overall, our results elucidated a critical pathway through which high CST1 expression protects gastric cancer cells from undergoing ferroptosis, thus promoting its progression and metastasis. CST1 may be used as a new oncological marker and potential therapeutic target for gastric cancer metastasis.

Characterization and Antibacterial Activity of a Polysaccharide Produced From Sugarcane Molasses by Chaetomium globosum CGMCC 6882.

As a by-product of the sugar industry containing many sugars, proteins, nitrogenous materials, and heavy metals, molasses is rarely used for polysaccharide production. In the present work, a Chaetomium globosum CGMCC 6882 polysaccharide was produced from sugarcane molasses (CGP-SM) was successfully produced from sugarcane molasses. The yield of CGP-SM was 5.83 ± 0.09 g/l and its protein content was 2.41 ± 0.12% (w/w). Structural analysis showed that CGP-SM was a crystalline and amorphous polysaccharide containing rhamnose, glucosamine, galactose, glucose, mannose, fructose, and glucuronic acid in the molar ratio of 10.31: 1.14: 2.07: 59.55: 42.65: 1.92: 9.63. Meanwhile, weight-average molecular weight (Mw), number-average molecular weight (Mn), and polydispersity (Mw/Mn) of CGP-SM were 28.37 KDa, 23.66 KDa, and 1.199, respectively. Furthermore, the bacteriostatic assay indicated that CGP-SM inhibited the growth of Escherichia coli and Staphylococcus aureus in a concentration-dependent manner, and its inhibitory effect on S. aureus was higher than that of E. coli. Above all, this work provides a green method for the production of bioactive polysaccharide from sugarcane molasses.

Characteristics and Evolution Mechanism of Three Phase Products of Lignite by Hydrothermal Treatment Dewatering.

Baiyinhua lignite was treated by hydrothermal treatment dewatering (HTD). The production characteristics of the gas, solid, and liquid were studied. Results show that HTD is an effective means to decrease water content and water-holding capacity. When the treatment temperature was increased to 310 °C, the moisture was reduced from 26.55% to 5.27%, and the dehydration rate reached 80.20%. At the same time, the carbon content and calorific value increased during the HTD process, which increased energy density. The H/C atomic ratio increased first, then decreased with the increasing temperature. The increase in the H/C atomic ratio was due to the breakdown of aromatic ether and formation of phenolic compounds at the low temperature. The phenolic compounds started to break at the high temperature, which resulted in the decrease in the H/C atomic ratio. These results can be proven by 13C NMR analysis. Combined with the analyses of calorific value, dehydration ratio, recovery of combustible product, and heat loss, the relative balance dehydration and deoxidation efficiency were evaluated, and 250 °C is a suitable temperature for the HTD process in lignite upgrading. The HTD process promoted the breakage and decomposition of weak chemical bonds in lignite, which resulted in many organic compounds in wastewater after the HTD process. The chemical oxygen demand and biochemical oxygen demand continually increase, and the biodegradability of the wastewater is relatively good. The index of biodegradability for wastewater is greater than 0.3 even at a hydrothermal treatment temperature of 310 °C. This indicates that wastewater can be subjected to biochemical treatment at a low treatment cost. At the same time, the metal ions and nonmetallic ions in wastewater and the gas component were studied. These research results aim to provide theoretical guidance for the industrialization of lignite hydrothermal modification.

The Effect of Hydrothermal Treatment on Structure and Flotation Characteristics of Lignite and a Mechanistic Analysis.

Lignite is difficult to obtain highly efficient indexes by conventional flotation due to its poor surface hydrophobicity. Although the modification of flotation reagents has made some progress in improving the flotation performance, they all remain at the stage in the laboratory. Here, we proposed to improve the flotation performance by hydrothermal treatment dewatering (HTD) for lignite. Combined with the 13C NMR and FT-IR analysis, the impact of the HTD process on lignite's chemical structural evolution and flotation performance was investigated. The results showed that the HTD process is an effective means for dehydration and deoxygenation to increase lignite quality and the metamorphic degree of coal. The content of oxygen-containing functional groups generally decreases during the HTD process, especially carboxyl acid and ether groups. Therefore, surface properties and wettability of HTD coal samples were changed, and the contact angle gradually increases with the HTD temperature increased, which enhance the hydrophobicity and decrease hydrophilia of the lignite surface. The HTD process effectively improves the flotation performance of lignite during the conventional flotation operation condition, even if the coal pulp after HTD was directly used as a flotation feedstock. Specifically, the coal oil and capryl alcohol were used as collector and forming agents, respectively, and the pulp concentration was adjusted to 60 g/L. The yield of the cleaned coal increased from 12.14% of the raw coal to 55.58% of HTD310, and combustible matter recovery increased from 13.83% of the raw coal to 65.17% of HTD310 by raw coal basis.