RESUMEN

Background: Natural killer (NK) cells play a significant role in anti-tumor immunity, and their involvement has been documented in various cancers. However, a deeper understanding of the mechanisms by which NK cells influence gastric cancer progression remains necessary. Methods: We utilized the Cancer Genome Atlas (TCGA) database to acquire transcriptional profiles, clinical information, and mutation data for gastric cancer patients. R software and associated packages were employed for all analyses of this publicly available data. Results: We used multiple algorithms to evaluate the tumor microenvironment in gastric cancer samples. We performed differential expression analysis to pinpoint genes related to NK cells. Utilizing this data, we developed a prognostic model featuring three crucial NK cell-related genes: MAB21L2, ARPP21, and MUCL1. This model showed strong predictive performance in the training and validation groups. Consistently, patients identified as high-risk according to our model had worse overall survival rates. To further elucidate the biological differences between high-risk and low-risk patients, we performed enrichment analyses focusing on biological pathways and immune-related factors. Additionally, we observed a correlation between higher risk scores and non-responsiveness to treatment. Interestingly, high-risk patients were found to be potentially more sensitive to axitinib. We selected MUCL1 for further investigation due to its potential role in the model. While MUCL1 mRNA levels were elevated in both gastric cancer and paired normal tissues, protein expression analysis using the Human Protein Atlas database revealed a decrease in MUCL1 protein levels within tumor tissues. Conclusions: Our findings contribute to a more comprehensive understanding of the role of NK cells in gastric cancer and highlight MUCL1 as a promising therapeutic target.

RESUMEN

BACKGROUND: Abnormal liver function was frequently observed in nonalcoholic fatty liver disease (NAFLD) patients infected with SARS-CoV-2. Our aim was to explore the effect of SARS-CoV-2 inactivated vaccines on liver function abnormality among NAFLD patients with COVID-19. METHODS: The multi-center retrospective cohort included 517 NAFLD patients with COVID-19 from 1 April to 30 June 2022. Participants who received 2 doses of the vaccine (n = 274) were propensity score matched (PSM) with 243 unvaccinated controls. The primary outcome was liver function abnormality and the secondary outcome was viral shedding duration. Logistic and Cox regression models were used to calculate the odds ratio (OR) and hazard ratio (HR) for the outcomes. Sensitivity analysis was conducted to assess robustness. FINDINGS: PSM identified 171 pairs of vaccinated and unvaccinated patients. Liver function abnormality was less frequent in the vaccinated group (adjusted OR, 0.556 [95% CI (confidence interval), 0.356-0.869], p = 0.010). Additionally, the vaccinated group demonstrated a lower incidence of abnormal bilirubin levels (total bilirubin: adjusted OR, 0.223 [95% CI, 0.072-0.690], p = 0.009; direct bilirubin: adjusted OR, 0.175 [95% CI, 0.080-0.384], p < 0.001) and shorter viral shedding duration (adjusted HR, 0.798 [95% CI, 0.641-0.994], p = 0.044) than the unvaccinated group. Further subgroup analysis revealed similar results, while the sensitivity analyses indicated consistent findings. INTERPRETATION: SARS-CoV-2 vaccination in patients with NAFLD may reduce the risk of liver dysfunction during COVID-19. Furthermore, vaccination demonstrated beneficial effects on viral shedding in the NAFLD population. FUNDING: 23XD1422700, Tszb2023-01, Zdzk2020-10, Zdxk2020-01, 2308085J27 and JLY20180124.

Asunto(s)

COVID-19 , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Vacunas contra la COVID-19 , Estudios Retrospectivos , COVID-19/complicaciones , COVID-19/prevención & control , SARS-CoV-2 , Bilirrubina , Vacunas de Productos Inactivados , Vacunación

RESUMEN

Circular RNAs (circRNAs) have been shown to play a crucial role in cancer occurrence and progression. This present work investigated the link between hsa_circ_0008234 and colon cancer. Data retrieved from GSE172229 was used to compare the circRNA profiles of colon cancer and surrounding non-tumorous tissues. The amount of RNA and protein in the molecules was determined using quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. The cell proliferation ability was assessed using CCK8, EdU, colon formation, and nude mice tumorigenesis tests. Cell invasion and migration abilities were evaluated using transwell wound healing and mice lung metastasis model. Hsa_circ_0008234 piqued our interest because bioinformatics and qRT-PCR analyses revealed that it is upregulated in colon cancer tissue. Cell phenotypic studies suggest that hsa_circ_0008234 may significantly increase colon cancer cell aggressiveness. Mice experiments revealed that inhibiting hsa_circ_0008234 significantly reduced tumor growth and metastasis. Moreover, the fluorescence in situ hybridization experiment demonstrated that hsa_circ_0008234 is primarily found in the cytoplasm, implying that it potentially functions via a competitive endogenous RNA pathway. These findings indicated that hsa_circ_0008234 may act as a "molecular sponge" for miR-338-3p, increasing the expression of miR-338-target 3p's ETS1. In addition, the traditional oncogenic pathway PI3K/AKT/mTOR signaling was found to be the potential downstream pathway of the hsa_circ_0008234/miR-338-3p/ETS1 axis. In conclusion, hsa_circ_0008234 increases colon cancer proliferation, infiltration, and migration via the miR-338-3p/ETS1/PI3K/AKT axis; therefore, it could serve as a target and a focus for colon cancer therapy.

RESUMEN

The wastes network system exploration in metallurgical process imposes of great significance for advancing green circular economy in steel plant. This paper originally proposes a closed-circulating CO2 sequestering process for wastes appreciation and harmless disposal, and the effect of two circulation strategy, i.e. Slag circulation strategy and cold-rolling waste water(CRW) circulation strategy, on the CO2 uptake efficiency, carbonation degree and desalination rate were systemically discussed. Then, their kinetics are analyzed by model and molecular simulation in detail, respectively. In addition, the energy consumption and the cost are simulated for comprehensively evaluating its superiority. The experimental and molecular simulation results all show that the peak values for both strategies could be achieved when circulation times is in the range of three to five. CRW circulation strategy has a better CO2 uptake efficiency than slag circulation strategy, the CO2 uptake efficiency is about 487kgCO2/tslag and corresponding desalination rate is 48.9%, when CRW is circulated for five times at 60 °C and 20 L/g for 90 min. Adopting CRW circulation strategy, the CO2 sequestration efficiency is averagely doubled comparing to previous results. 129%-183% energy consumption and 35.6% cost would be reduced, which represents that the proposed routine is economical to step forward to industrial application.