Amniotic fluid metabolic fingerprinting contributes to shaping the unfavourable intrauterine environment in monochorionic diamniotic twins.

BACKGROUND & AIMS: Amniotic fluid (AF) is the primary intrauterine environment for fetal growth throughout gestation. Selective fetal growth restriction (sFGR) is an adverse complication characterized by unequal growth in twins with nearly identical genetic makeup. However, the influence of AF-mediated intrauterine environment on the development and progression of sFGR remains unexplored. METHODS: High-throughput targeted metabolomics analysis (G350) was performed on AF samples collected from sFGR (n = 18) and MCDA twins with birth weight concordance (MCDA-C, n = 20) cases. Weighted correlation network analysis (WGCNA) was used to identify clinical features that may influence the metabolite composition in AF. Subsequently, partial least-squares discriminant analysis (PLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to compare the different types of sFGR and MCDA-C twins. Receiver operating characteristic (ROC) and multivariate ROC curves were utilized to explore potential AF markers in twins with sFGR. RESULTS: In our study, 182 metabolites were quantified in 76 AF samples. WGCNA indicated that the metabolite composition in late AF may not be influenced by gestational age. PLSDA demonstrated distinct variations between the metabolite profiles of AF in the sFGR and MCDA-C twins, with a significant emphasis on amino acids as the primary differential metabolite. The dissimilarities observed in sFGR twins were predominantly attributed to lipid metabolism-related metabolites. In particular, the KEGG enrichment metabolic pathway analysis revealed significant associations of both types of sFGR twins with central carbon metabolism in cancer. The multivariate ROC curves indicated that the combination of carnosine, sarcosine, l-alanine, beta-alanine, and alpha-n-phenylacetylglutamine significantly improved the AUC to 0.928. Notably, the ROC curves highlighted creatine (AUC:0.934) may be a potential biomarker for severe sFGR. CONCLUSION: The data presented in this study offer a comprehensive metabolic map of the AF in cases of sFGR, shedding light on potential biomarkers associated with fetal growth and development in MCDA twins.

Botrysphin D attenuates arsenic-induced oxidative stress in human lung epithelial cells via activating Nrf2/ARE signaling pathways.

Oxidative stress is one of the main pathogenesis for many human diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays a key role in regulating intracellular antioxidant responses, and thus activation of Nrf2/ARE signaling pathway is a potential chemopreventive or therapeutic strategy to treat diseases caused by oxidative damage. In the present study, we have found that treatment of Beas-2B cells with botrysphins D (BD) attenuated sodium arsenite [As (III)]-induced cell death and apoptosis. Meanwhile, BD was able to upregulate protein levels of Nrf2 and its downstream genes NQO1 and γ-GCS through inducing Nrf2 nuclear translocation, enhancing protein stability, and inhibiting ubiquitination. It was also found that BD-induced activation of the Nrf2/ARE pathway was regulated by PI3K, MEK1/2, PKC, and PERK kinases. Collectively, BD is a novel activator of Nrf2/ARE pathway, and is verified to be a potential preventive agent against oxidative stress-induced damage in human lung tissues.

Diagnosis and survival values of neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in esophageal cancer.

BACKGROUND: Recent studies have borne out claims that inflammation has a vital role in the development and progression of many diseases, including cancers. It has been reported that neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) could act as independent prognostic factors for several malignant tumors. We evaluated the diagnosis and prognosis values of preoperative inflammatory indicators, including NLR and RDW in esophageal cancer (EC). METHODS: We retrospectively analyzed the clinical data of 354 EC patients and 220 early esophageal cancer (EEC) undergoing potentially curative esophagectomy in Shandong Provincial Hospital Affiliated to Shandong University and chose 201 age and sex-matched healthy volunteers as the control group. We compared the clinicopathological features, survival curves and prognosis of the EC patients between the high and low groups according to the cutoff values of NLR and RDW. RESULTS: Significant higher preoperative NLR and RDW values were detected in patients with EEC and EC compared to the healthy controls (P < .001). A high RDW was significantly associated with an older age (P < .05). NLR and RDW values after surgery in EC group were significantly higher than those before surgery (P < .001 and P < .001, respectively). For EEC group, a higher RDW value showed a significantly worse overall survival (OS) and disease-free survival (DFS) (P = .040 and P = .013, respectively). For EC group, an increased NLR indicated a significantly association with poor overall survival (OS) (P = .004) and DFS (P = .001). Preoperative NLR can act as an independent prognostic indicator for EC. CONCLUSION: The preoperative NLR and RDW are convenient, practical easily measured biomarkers of clinical diagnosis and prognostic assessment of patients with EC. Furthermore, NLR was more effective than RDW acting as an independent prognostic biomarker for EC.

MDA-19 Suppresses Progression of Melanoma Via Inhibiting the PI3K/Akt Pathway.

OBJECTIVE: To investigate the effect of MDA-19 on progression of melanoma, and explore the relevant mechanism. METHODS: The melanoma cell lines, M14 and UACC257, were treated with different concentrations of MDA-19, then CCK8, clone formation assay, Transwell and flow cytometry assays were performed to examine cell proliferation, migration, invasion and apoptosis, respectively. The expression of apoptosis-related proteins (Bcl-2, Bax and caspase 3 P17), EMT and signaling pathway-related proteins were also detected by Western blot. RESULTS: MDA-19 inhibited melanoma cells in a dose-dependent manner. Compared to the NC group, MDA-19 significantly inhibited cell growth capacity, migration and invasion of M14 and UACC257 cells, and accelerated cell apoptosis in a mitochondrial pathway through regulating Bcl-2/Bax and Caspase 3 in M14 and UACC257 cells. Moreover, MDA-19 was observed to up-regulate the expression of E-cad and down-regulate the expression of N-cad, Vimentin and Slug in melanoma cells in vitro. Furthermore, MDA-19 could inhibit the PI3K/Akt pathway by blocking Akt phosphorylation (p-Akt) and downstream proteins, P70 and Cyclin D1 in M14 and UACC257 cells. CONCLUSION: Our data demonstrate that MDA-19 could inhibit progression of melanoma by suppressing the PI3K/Akt pathway, suggesting that MDA-19 is a potential anti-cancer agent for therapy of melanoma.

Clinical implications of pretreatment inflammatory biomarkers as independent prognostic indicators in prostate cancer.

OBJECTIVES: Research on the relationship between inflammatory biomarkers and malignant tumors has become a hotspot. Many studies have demonstrated that neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) could act as independent prognostic indicators for several solid tumors. This study aimed to evaluate the clinical implications of pretreatment inflammatory biomarkers, including NLR, PLR, and RDW as independent prognostic indicators in prostate cancer (PCa). METHODS: A total of 226 PCa patients who were diagnosed at our institution from 2011 to 2016 were analyzed retrospectively. We compared the clinicopathological features, survival curves, and prognosis of the PCa patients between the high and low groups according to the cutoffs of NLR, PLR, and RDW. RESULTS: The pretreatment NLR, PLR, and RDW values were significantly higher in the patients with PCa than those in the controls (P<.05). Increased NLR and PLR values were significantly associated with high risk of progression, including higher Gleason scores, cell proliferation antigen 67 (Ki-67) indexes, and prostate-specific antigen (PSA) levels (P<.05), whereas an elevated RDW was only associated with an older age. An increased NLR was correlated with both overall survival (OS) (P=.025) and disease-free survival (DFS) (P=.017). In addition, a higher PLR only showed a significantly worse DFS (P=.040). Pretreatment NLR was an independent prognostic indicator of DFS. CONCLUSIONS: The pretreatment NLR and PLR might be beneficial to predict the progression and prognosis of PCa. Furthermore, NLR was more effective than PLR acting as an independent prognostic indicator for PCa.