Multi-Omics Analysis Reveals the Role of Changes in Platelet Activation Pathways in the Survival Outcome of Patients with Esophageal Squamous Cell Carcinoma.

Objective: The objective of this study was to integrate metabolomics and transcriptomics data to identify key diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected from 85 ESCC patients at different stages and 50 healthy volunteers for non-targeted metabolomic analysis. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for non-targeted metabolomic analysis. Subsequently, we integrated the metabolomic data with transcriptomic data from the Gene Expression Omnibus (GEO) and prognosis data from The Cancer Genome Atlas Program (TCGA) to perform pathway analysis. Our focus was on pathways that involve both metabolites and upstream genes, as they often exhibit higher accuracy. Results: Through the integration of metabolomics and transcriptomics, we identified significant alterations in the platelet activation pathway in ESCC. This pathway involves the participation of both metabolites and genes, making it a more accurate reflection of pathological changes associated with the disease. Notably, metabolite arachidonic acid (AA) and chemokine receptor type 2(CXCR2) were significantly downregulated in ESCC, while genes collagen type I alpha 1(COL1A1), collagen type I alpha 2(COL1A2), collagen type III alpha 1(COL3A1), type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), and insulin-like growth factor II mRNA binding protein 3(IGF2BP3) were significantly upregulated, indicating the presence of tumor-induced platelet activation in ESCC. Further analysis of prognosis data revealed that high expression of COL1A1, IGF2BP3, and ITPR3 was associated with a favorable prognosis for ESCC, while high CXCR2 expression was linked to an adverse prognosis. In addition, we combined COL1A1, ITPR3, IGF2BP3, CXCR2, and AA to form a diagnostic biomarker panel. The receiver operating characteristic curve (ROC) demonstrated excellent diagnostic capability (AUC=0.987). Conclusion: Our study underscores the significant role of platelet activation pathways and related genes in the diagnosis and prognosis of ESCC patients. These findings offer promising insights for improving the clinical management of ESCC.

Self-assembled albumin nanoparticles induce pyroptosis for photodynamic/photothermal/immuno synergistic therapies in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized by a high degree of malignancy, early metastasis, limited treatment, and poor prognosis. Immunotherapy, as a new and most promising treatment for cancer, has limited efficacy in TNBC because of the immunosuppressive tumor microenvironment (TME). Inducing pyroptosis and activating the cyclic guanosine monophosphate-adenosine monophosphate synthase/interferon gene stimulator (cGAS/STING) signaling pathway to upregulate innate immunity have become an emerging strategy for enhancing tumor immunotherapy. In this study, albumin nanospheres were constructed with photosensitizer-IR780 encapsulated in the core and cGAS-STING agonists/H2S producer-ZnS loaded on the shell (named IR780-ZnS@HSA). In vitro, IR780-ZnS@HSA produced photothermal therapy (PTT) and photodynamic therapy (PDT) effects. In addition, it stimulated immunogenic cell death (ICD) and activated pyroptosis in tumor cells via the caspase-3-GSDME signaling pathway. IR780-ZnS@HSA also activated the cGAS-STING signaling pathway. The two pathways synergistically boost immune response. In vivo, IR780-ZnS@HSA + laser significantly inhibited tumor growth in 4T1 tumor-bearing mice and triggered an immune response, improving the efficacy of the anti-APD-L1 antibody (aPD-L1). In conclusion, IR780-ZnS@HSA, as a novel inducer of pyroptosis, can significantly inhibit tumor growth and improve the efficacy of aPD-L1.

Spatiotemporal dynamics and anthropologically dominated drivers of chlorophyll-a, TN and TP concentrations in the Pearl River Estuary based on retrieval algorithm and random forest regression.

Estimation of large-scale and high-precision water quality parameters is critical in explaining the spatiotemporal dynamics and the driving factors of water quality variability, especially in areas with environmental complexity (e.g., crisscrossing waterways, high flood risk in rainy season and seawater invasion). Thus, in this study, a retrieval algorithm was developed to predict chlorophyll-a (Chl-a), total nitrogen (TN) and total phosphorus (TP) concentrations in the Pearl River Estuary (PRE) based on a large amount of in situ measurements and Landsat 8 remote sensing images. Random Forest (RF) machine learning was conducted to identify the relationship between environmental indicators (pH, turbidity, conductivity, total dissolved solids and water temperature), Chl-a, TN and TP. The results showed that the NIR/R Binomial algorithm for Chl-a estimation presented appreciable reliability with R2 of 0.7429, root mean square error (RMSE) of 1.2089 and mean absolute percent error (MAPE) of 15.33%. The water quality variation in the PRE showed a characteristic of overall improvement and regional deterioration with average concentrations of 7.28 µg/L, 1.15 mg/L and 0.12 mg/L for Chl-a, TN, and TP respectively. Turbidity and pH were identified as the most important indicators to explain Chl-a (52.86%, 39.91%), TN (52.38%, 40.57%) and TP (55.23%, 40.03%) variation. Agricultural pollution was the main pollution source due to the intensive application of fertilizer and increased field size. Besides, land use patterns (e.g., increasing farmland but decreasing forest) greatly influenced water quality from 2010 to 2020. Moreover, light limitation caused by high turbidity reduced the algae productivity and further lowered the Chl-a concentration. The driving factors for regional water quality variations were anthropologically dominated and supplemented by climate change. This study improved the monitoring accuracy of regional water environment and provided quantitative early warning of water pollution events for environmental practitioners, so as to achieve long-term monitoring, precise pollution management and efficient water resources management.

Sulfation of Quercitrin, Epicatechin and Rutin by Human Cytosolic Sulfotransferases (SULTs): Differential Effects of SULT Genetic Polymorphisms.

Radix Bupleuri is one of the most widely used herbal medicines in China for the treatment of fever, pain, and/or chronic inflammation. Quercitrin, epicatechin, and rutin, the flavonoids present in Radix Bupleuri, have been reported to display anti-inflammatory, antitumor, and antioxidant biological activities among others. Sulfation has been reported to play an important role in the metabolism of flavonoids. In this study, we aimed to systematically identify the human cytosolic sulfotransferase enzymes that are capable of catalyzing the sulfation of quercitrin, epicatechin, and rutin. Of the thirteen known human cytosolic sulfotransferases, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1C2, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward quercitrin, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A3, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward epicatechin, and six (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A2, cytosolic sulfotransferase 1A3, cytosolic sulfotransferase 1B1, cytosolic sulfotransferase 1C4, and cytosolic sulfotransferase 1E1) displayed sulfating activity toward rutin. The kinetic parameters of the cytosolic sulfotransferases that showed the strongest sulfating activities were determined. To investigate the effects of genetic polymorphisms on the sulfation of quercitrin, epicatechin, and rutin, individual panels of cytosolic sulfotransferase allozymes previously prepared were analyzed and shown to display differential sulfating activities toward each of the three flavonoids. Taken together, these results provided a biochemical basis underlying the metabolism of quercitrin, epicatechin, and rutin through sulfation in humans.

Effect of the polyphenol-rich extract from Allium cepa on hyperlipidemic sprague-dawley rats.

Allium cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. This study was mainly aimed at investigating the effects of A. cepa extract (ACE) enriched in polyphenols on hyperlipidemia Sprague-Dawley (SD) experiment rat models. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), and superoxide dismutase (SOD) activity in serum and liver were measured using ELISA kits. In addition, hematoxylin-eosin (HE) technique was used to observe the liver and the aortic arch pathology. Moreover, western blotting (WB) method was applied to analyze LDL receptor (LDLR) and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HMGCR) in liver. As a result, quercetin (2.42 mg/g DW) and isoquercitrin (4.60 mg/g DW) were the main constituents of ACE using HPLC analysis. Furthermore, ACE reduced the levels of TC, TG, LDL-C, and MDA, and increased HDL levels and elevated SOD activity both in serum and liver in hyperlipidemic SD rats (p < .05). HE results showed that liver fat drops of the rats in ACE group were obviously decreased, and the lipid and foam cells of the aortic arch of the rats in ACE group were markedly ameliorated. WB results showed that ACE promoted the degradation of HMGCR and increased LDLR expression in liver (p < .05). In conclusion, ACE alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR. PRACTICAL APPLICATIONS: Atherosclerosis, a major cardiovascular disease, is the leading cause of mortality and morbidity in the developed countries. Moreover, accumulating data indicate that, during atherosclerosis development, hyperlipidemia is an important risk factor. To date, hyperlipidemia is mainly treated with hyperlipidemic agents including statins, in spite of the side effects and poor tolerance in some patients. In addition, Allium cepa is a medicinal and edible plant. Furthermore, A. cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. But the underlying mechanism is still unclear. In fact, this research showed that A. cepa extract (ACE) alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR, suggesting that ACE might be a potential option for hyperlipidemia as non-statin lipid-lowering agent.

The lipid-lowering effects of Danhong and Huangqi injections: a meta-analysis of clinical controlled trials.

BACKGROUND: Dyslipidaemia is a major risk factor for coronary heart disease (CHD). Danhong and Huangqi injections, two traditional Chinese medicine prescriptions, have been widely studied regarding their lipid-lowering properties. However, the results were inconsistent and inconclusive. Thus, we conducted this meta-analysis of clinical controlled trials to clarify the lipid-lowering effects of Danhong and Huangqi injections. METHODS: The databases including PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang Database, CNKI and VIP were searched. The following information was obtained from each study: first author, age, gender, ethnicity, health condition, treatment dose, treatment duration, sample size, mean and standard deviation or standard error of lipid variables before and after treatment. The changes in lipid levels from pre- to post-treatment were calculated and compared between the control groups and the treatment groups in this meta-analysis. RESULTS: Forty-four studies (5021 subjects) and 7 studies (542 subjects) were respectively identified for Danhong and Huangqi injections. Compared with the control groups, Danhong injection yielded a significant reduction in triglycerides (TG) [standardized mean difference (SMD) = - 0.76, 95% confidence interval (CI) = (- 0.91, - 0.61), P <  0.001], total cholesterol (TC) [SMD = - 1.29, 95% CI = (- 1.56, - 1.03), P <  0.001] and low-density lipoprotein cholesterol (LDL-C) [SMD = - 0.76, 95% CI = (- 0.93, - 0.59), P <  0.001], and a significant elevation in high-density lipoprotein cholesterol (HDL-C) [SMD = 0.70, 95% CI = (0.41, 0.98), P <  0.001]. Regarding Huangqi injection, it yielded a significant reduction in TC [SMD = - 1.13, 95% CI = (- 2.09, - 0.16), P = 0.02] and marginally in TG [SMD = - 1.27, 95% CI = (- 2.53, 0.00), P = 0.05] comparing with the control groups. CONCLUSIONS: Danhong injection can effectively decrease the plasma levels of TG, TC and LDL-C, and increase HDL-C levels. Huangqi injection also has significant effects on TG and TC reduction, but not as powerful as Danhong injection.

Sulfate conjugation of daphnetin by the human cytosolic sulfotransferases.

ETHNOPHARMACOLOGICAL RELEVANCE: In Turkey, daphnetin-containing Daphne oleoides is used as a folk medicine for treating rheumatic pain and lumbago. A daphnetin-containing traditional Chinese medicine tablet, named Zushima-Pian, is available in China for treating rheumatoid arthritis. The present study aimed to investigate the metabolism of daphnetin through sulfation in cultured human cells and to identify the human cytosolic sulfotransferase(s) (SULT(s)) that is(are) capable of mediating the sulfation of daphnetin. MATERIALS AND METHODS: Cultured HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells were labeled with [(35)S]sulfate in the presence of different concentrations of daphnetin. Thirteen known human SULTs, previously expressed and purified, as well as cytosols of human kidney, liver, lung, and small intestine, were examined for daphnetin-sulfating activity using an established sulfotransferase assay. RESULTS: [(35)S]sulfated daphnetin was found to be generated and released by HepG2 cells and Caco-2 cells labeled with [(35)S] sulfate in the presence of daphnetin. Among the 13 known human SULTs, SULT1A1, SULT1A2, SULT1A3, SULT1B1, and SULT1C4 displayed significant sulfating activity toward daphnetin. Of the four human organ samples later tested, small intestine and liver cytosols displayed considerably higher daphnetin-sulfating activity than those of lung and kidney. CONCLUSION: The results derived from the present study showed unequivocally that daphnetin could be sulfated in cultured human cells and by purified human SULT enzymes as well as human organ cytosols. The information obtained provided a basis for further studies on the metabolism of daphnetin through sulfation in vivo.

Sulfation of 6-Gingerol by the Human Cytosolic Sulfotransferases: A Systematic Analysis.

Previous studies have demonstrated the presence of the sulfated form of 6-gingerol, a major pharmacologically active component of ginger, in plasma samples of normal human subjects who were administered 6-gingerol. The current study was designed to systematically identify the major human cytosolic sulfotransferase enzyme(s) capable of mediating the sulfation of 6-gingerol. Of the 13 known human cytosolic sulfotransferases examined, six (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C4, SULT1E1) displayed significant sulfating activity toward 6-gingerol. Kinetic parameters of SULT1A1, SULT1A3, SULT1C4, and SULT1E1 that showed stronger 6-gingerol-sulfating activity were determined. Of the four human organ samples tested, small intestine and liver cytosols displayed considerably higher 6-gingerol-sulfating activity than those of the lung and kidney. Moreover, sulfation of 6-gingerol was shown to occur in HepG2 human hepatoma cells and Caco-2 human colon adenocarcinoma cells under the metabolic setting. Collectively, these results provided useful information relevant to the metabolism of 6-gingerol through sulfation both in vitro and in vivo.