Fusobacterium periodonticum BCT protein targeting glucose metabolism to promote the epithelial-mesenchymal transition of esophageal cancer cells by lactic acid.

BACKGROUND: The cancer microbiota was considered the main risk factor for cancer progression. We had proved that Fusobacterium periodonticum (F.p) was higher abundance in Esophageal cancer(EC)tissues. Bioinformation analysis found that BCT was a key virulence protein of F.p. However, little is known about the role and mechanism of BCT in EC. This study aimed to recognize the key virulence protein of F.p and explore the mechanism of BCT in promoting EC. METHODS: We constructed a eukaryotic expression vector and purified the recombinant protein BCT. CCK8 used to analyzed the activity of EC after treated by different concentration of BCT. UPLC-MS/MS and ELISA used to detect the metabonomics and metabolites. The ability of migration and invasion was completed by transwell assay. RT-QPCR, WB used to analyze the expression of relevant genes. RESULTS: Our data showed that BCT was higher expression in EC tumor tissues (p < 0.05) and BCT in 20 µg/mL promoted the survival, invasion and migration of EC cells (EC109) (p < 0.05). Meanwhile, UPLC-MS/MS results suggested that BCT resulted in an augmentation of hypotaurine metabolism, arachidonic acid metabolism, glycolysis/gluconeogenesis, tryptophan metabolism, citrate cycle activity in EC109. The metabolic changes resulted in decreasing in glucose and pyruvate levels but increase in lactate dehydrogenase (LDH) activity and lactic acid (LA) as well as the expression of glucose transporter 1, Hexokinase 2, LDH which regulated the glycolysis were all changed (p < 0.05). The BCT treatment upregulated the expression of TLR4, Akt, HIF-1α (p < 0.05) which regulated the production of LA. Furthermore, LA stimulation promoted the expression of GPR81, Wnt, and ß-catenin (p < 0.05), thereby inducing EMT and metastasis in EC109 cells. CONCLUSION: Altogether, these findings identified that impact of BCT in regulation of glycolysis in EC109 and its involves the TLR4/Akt/HIF-1α pathway. Meanwhile, glycolysis increasing the release of LA and promote the EMT of EC109 by GPR81/Wnt/ß-catenin signaling pathway. In summary, our findings underscore the potential of targeting BCT as an innovative strategy to mitigate the development of EC.

Association between ambient air pollutants and lipid profile: A systematic review and meta-analysis.

BACKGROUND: Studies of the effects of atmospheric pollutants on lipid profiles remain inconsistent and controversial. AIM: The study was aimed to investigate the relationship between the exposure to ambient air pollutants and variations in the blood lipid profiles in the population. METHODS: A comprehensive search of three different databases (PubMed, Web of Science, and the Cochrane Library) until December 17, 2022, yielded 17 origional studies fulfilling the inclusion criteria for a meta-analysis. Aggregate effect measures and 95% confidence intervals (95% CI) for the relevant ambient air pollutants were deduced employing random effects models. RESULTS: The collective meta-analysis indicated that long-term exposure to PM1, PM2.5, PM10 and CO showed a substantial correlation with TC (PM1: ß = 2.04, 95%CI = 0.15-3.94; PM2.5: ß = 1.11, 95%CI = 0.39-1.84; PM10: ß = 1.70, 95%CI = 0.67-2.73; CO: ß = 0.08, 95%CI = 0.06-0.10), PM10 exhibited a significant association with TG (ß = 0. 537,95% CI = 0.09-0.97), whereas HDL-C demonstrated notable relationships with PM1, PM10, SO2 and CO (PM1: ß = -2.38, 95%CI = -4.00 to -2.76; PM10: ß = -0.77, 95%CI = -1.33 to -0.21; SO2: ß = -0.91, 95%CI = -1.73 to -0.10; CO: ß = -0.03, 95%CI = -0.05 to 0.00). PM2.5, PM10 also showed significant associations with LDL-C (PM2.5: ß = 1.44 95%CI = 0.48-2.40; PM10: ß = 1.62 95%CI = 0.90-2.34). Subgroup analysis revealed significant or stronger correlations predominantly in cohort study designs, with higher male comparisons, and in regions exhibiting elevated contaminant levels. CONCLUSION: In summary, the analysis substantiates that ambient air pollutants can be recognized as potent contributors to alterations in lipid profiles, particularly particulate pollutants which exert more obvious effects on lipid profiles.

A critical review of advances in tumor metabolism abnormalities induced by nitrosamine disinfection by-products in drinking water.

Intensified sanitation practices amid the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak might result in the increased release of chloramine disinfectants into surface water, significantly promoting the formation of nitrosamine disinfection by-products (DBPs) in drinking water. Unfortunately, these nitrosamine DBPs exhibit significant genotoxic, carcinogenic, and mutagenic properties, whereas chlorinating disinfectants remain in global practice. The current review provides valuable insights into the occurrence, identification, contamination status, exposure limits, and toxicity of the new unregulated disinfection by-products (nitrosamine DBPs) in drinking water. As a result, concentrations of nitrosamine DBPs far exceed allowable limits in drinking water, and prolonged exposure has the potential to cause metabolic disorders, a critical step in tumor initiation and progression. Importantly, based on recent research, we have concluded the role of nitrosamines DBPs in different metabolic pathways. Remarkably, nitrosamine DBPs can induce chronic inflammation and initiate tumors by activating sphingolipid and polyunsaturated fatty acid metabolism. Regarding amino acid and nucleotide metabolism, nitrosamine DBPs can inhibit tryptophan metabolism and de novo nucleotide synthesis. Moreover, inhibition of de novo nucleotide synthesis fails to repair DNA damage induced by nitrosamines. Additionally, the accumulation of lactate induced by nitrosamine DBPs may act as a pivotal signaling molecule in communication within the tumor microenvironment. However, with the advancement of tumor metabolomics, understanding the role of nitrosamine DBPs in causing cancer by inducing metabolic abnormalities significantly lags behind, and specific mechanisms of toxic effects are not clearly defined. Urgently, further studies exploring this promising area are needed.

Zinc deficiency drives ferroptosis resistance by lactate production in esophageal squamous cell carcinoma.

Trace metal zinc is involved in key processes of solid tumors by its antioxidant properties, while the role of zinc at the onset of esophageal squamous cell carcinoma (ESCC) remains controversial. This study aimed to determine whether zinc is associated with the ESCC and underlying molecular events involving malignant progression. Based on a case-control study, we found serum and urine zinc were decreased and correlated with ESCC progression. Thus, an in vitro model for zinc deficiency (ZD) was established, and we found that ZD contributed to the proliferation, migration, and invasion of EC109 cells. Untargeted metabolomics identified 59 upregulated metabolites and 6 downregulated metabolites, among which glycolysis and ferroptosis-related oxidation of chain fatty acids might play crucial steps in ZD-treated molecular events. Interestingly, ZD disrupted redox homeostasis and enhanced cytosolic Fe2+ of EC109 cells, while lipid peroxidation, the key marker of ferroptosis occurrence, was decreased after ZD treatment. The mechanism underlying these changes may involve ZD-enhanced ESCC glycolysis and lactate production, which confer ferroptosis resistance by inhibiting of p-AMPK and leading to the upregulation of SREBP1 and SCD1 to enhance the production of anti-ferroptosis monounsaturated fatty acids.

The mediating role of AKT/ERK/JNK signaling on the malignant phenotype of microcystin-LR in gastric adenocarcinoma cells.

Microcystin-leucine arginine (MC-LR), a widely distributed and highly toxic environmental pollutant, plays crucial roles in cancer malignancy by activating characteristically toxic signaling pathways. Traditional animal-based toxicity evaluation methods have proven insufficient for identifying the specific role of these signaling pathways. Therefore, this study aimed to uncover the regulatory relationship between the toxic pathways and the progression of gastric cancer (GC). The findings provide novel avenues for conducting in vitro toxicity tests based on the investigated pathways. We found that MC-LR promoted the migration and invasion of SGC-7901 cells while simultaneously inhibiting their apoptosis in a dose-dependent manner. This observed cytotoxicity was primarily mediated through the AKT, JNK, and ERK signaling pathways. By using a mediation analysis model, we determined that AKT and ERK exhibited competitive effects in MC-LR-treated GC malignancy, while AKT and JNK acted independently from one another. This study establishes an in vitro toxicity test model of MC-LR based on toxicity-related pathways and underscores the pivotal roles of AKT, ERK, and JNK signaling in MC-LR toxicity. The findings offer a novel, fundamental framework for conducting chemical toxicity risk assessment.

Comprehensive proteomic and phosphoproteomic reveal that Microcystin-LR contributed to the malignant progression of gastric cancer by estrogenic potency.

The widespread cyanotoxins in drinking water pose a threat to public health induced by Microcystins (MCs). MC-LR, a predominant toxic form of MCs, has been found to play critical roles in cancer progression. The role of MC-LR in hepatocarcinogenesis has attracted extensive attention. However, as a critical digestive organ, the precise mechanism of MC-LR-induced gastric cancer is still unclear. We found that 100 nM MC-LR promoted the proliferation, migration, invasion, and anti-apoptosis of SGC-7901 cells. Quantitative proteome and phosphoproteome analysis identified differential expression patterns and aberrant pathways of SGC-7901 cells exposed to MC-LR. The results indicated that 48,109 unique peptides from 6320 proteins and 1375 phosphoproteins with 3473 phosphorylation sites were detected after 24 h treatment of MC-LR. Proteome and phosphoproteome conjoint analysis indicated estrogen signaling pathway might play an essential step in MC-LR-treated molecular events. The mechanism underlying these changes may involve MC-LR excessively activating the estrogen signaling pathway by reducing Hsp90 phosphorylation, which results in nucleus translocation of activated ERα and Krt16 overexpression in gastric cells. In general, our results indicate multiple crucial signals triggered by MC-LR, among which MC-LR may promote the development of gastric cancer by exerting estrogenic potency.

Ultrasonic-Vibration-Assisted Waterjet Drilling of [0/45/-45/90]2s Carbon-Fiber-Reinforced Polymer Laminates.

The pure waterjet (WJ) drilling process of carbon-fiber-reinforced polymer (CFRP) laminates causes damage, such as tears and delamination, leading to poor-quality hole-wall. Ultrasonic-vibration-assisted technology can improve the quality of hole walls and repair such damage, particularly the delamination of CFRP laminates. In this study, we conducted a numerical and experimental investigation of a high-pressure pure WJ drilling process of CFRP laminates performed using ultrasonic vibration to improve the delamination phenomena of the pure WJ drilling process. An explicit dynamic model using the smoothed particle hydrodynamics method was employed to simulate the ultrasonic-vibration-assisted WJ drilling of CFRP laminates and ascertain the optimal drilling performance. Thereafter, WJ drilling experiments were conducted to verify the numerical simulation. The results illustrate that the employment of ultrasonic vibration significantly increased the material removal rate by approximately 20%. Moreover, the water-wedging action that induces the propagation of delamination was weakened with an increase in the amplitude of the ultrasonic vibration. The hole-wall quality was optimal with the following drilling parameters: amplitude, 10 µm; frequency, 20 kHz; and WJ velocity, 900 m/s. The delamination zone length was only 0.19 mm and was reduced by 85.6% compared with the values obtained using non-assisted WJ drilling.

A Probabilistic Method for Image Enhancement With Simultaneous Illumination and Reflectance Estimation.

In this paper, a new probabilistic method for image enhancement is presented based on a simultaneous estimation of illumination and reflectance in the linear domain. We show that the linear domain model can better represent prior information for better estimation of reflectance and illumination than the logarithmic domain. A maximum a posteriori (MAP) formulation is employed with priors of both illumination and reflectance. To estimate illumination and reflectance effectively, an alternating direction method of multipliers is adopted to solve the MAP problem. The experimental results show the satisfactory performance of the proposed method to obtain reflectance and illumination with visually pleasing enhanced results and a promising convergence rate. Compared with other testing methods, the proposed method yields comparable or better results on both subjective and objective assessments.