A New Method of Extracting Polygonatum sibiricum Polysaccharide with Antioxidant Function: Ultrasound-Assisted Extraction-Deep Eutectic Solvents Method.

Polygonatum sibiricum Polysaccharide (PsP) with antioxidant function is the main active component of Polygonatum sibiricum (P.sibiricum). The currently poor extraction yield and extraction methods of PsP cannot meet the application of that in food industrial production. In this research, an ultrasound-assisted extraction-deep eutectic solvents (UAE-DESs) method, which has never been used in the PsP industry, was first used to extract PsP. The extraction conditions were optimized by the response surface method (RSM). Both the extraction yield and antioxidant function were simultaneously considered during the optimization process. The indicators of PsP's level and antioxidant activity in vitro were used to present the extraction yield of the UAE-DESs method, the purity, and the antioxidant effect of PsP. Under the optimal conditions, which included a liquid-solid ratio of 26:1 (mL:g), extraction temperature of 80 °C, ultrasonic time of 51 min, and ultrasonic power of 82 W, the PsP extraction yield could reach (43.61 ± 0.09)%, which was obviously higher than single DESs (33.81%) and UAE (5.83%), respectively, and the PsP appeared favorably antioxidant function. This research proposed an efficient extraction method for PsP, filled the basic research gap, and further improved the development of PsP as a dietary supplement with antioxidant function in the food industry.

Precious-Metal-Free CO2 Photoreduction Boosted by Dynamic Coordinative Interaction between Pyridine-Tethered Cu(I) Sensitizers and a Co(II) Catalyst.

Improving the photocatalytic efficiency of a fully noble-metal-free system for CO2 reduction remains a fundamental challenge, which can be accomplished by facilitating electron delivery as a consequence of exploiting intermolecular interactions. Herein, we have designed two Cu(I) photosensitizers with different pyridyl pendants at the phenanthroline moiety to enable dynamic coordinative interactions between the sensitizers and a cobalt macrocyclic catalyst. Compared to the parent Cu(I) photosensitizer, one of the pyridine-tethered derivatives boosts the apparent quantum yield up to 76 ± 6% at 425 nm for selective (near 99%) CO2-to-CO conversion. This value is nearly twice that of the parent system with no pyridyl pendants (40 ± 5%) and substantially surpasses the record (57%) of the noble-metal-free systems reported so far. This system also realizes a maximum turnover number of 11 800 ± 1400. In contrast, another Cu(I) photosensitizer, in which the pyridine substituents are directly linked to the phenanthroline moiety, is inactive. The above behavior and photocatalytic mechanism are systematically elucidated by transient fluorescence, transient absorption, transient X-ray absorption spectroscopies, and quantum chemical calculations. This work highlights the advantage of constructing coordinative interactions to fine-tune the electron transfer processes within noble-metal-free systems for CO2 photoreduction.

Prognostic significance of carboxypeptidase Q and its methylation in glioblastoma.

Background: Glioblastoma (GBM) is a highly aggressive intracranial malignant tumor. The role of carboxypeptidase Q (CPQ) in GBM remains unknown. This study was to investigate the prognostic significance of CPQ and its methylation in GBM. Methods: We collected data from The Cancer Genome Atlas (TCGA)-GBM database and analyzed the different expression of CPQ in GBM tissues and normal tissues. Then we explored the correlation of CPQ mRNA expression and DNA methylation, and confirmed the prognostic significance of them based on six additional datasets from TCGA, The Chinese Glioma Genome Atlas (CGGA) and Gene Expression Omnibus (GEO) databases. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis were utilized to investigate the biological function of CPQ in GBM. Furthermore, we determined the association of CPQ expression and immune cell infiltration, immune markers and tumor microenvironment using different bioinformatic algorithms. R (version 4.1) and GraphPad Prism (version 8.0) were used to analyze the data. Results: CPQ mRNA expression in GBM tissues was significantly higher than that in normal brain tissues. DNA methylation of CPQ was negatively correlated with its expression. Patients with low CPQ expression or higher CPQ methylation level had remarkably better overall survival (OS). The TOP20 biological processes relevant to the differentially expressed genes between high and low CPQ patients were almost all related to immunity. And the differentially expressed genes were involved in several immune-related signaling pathways. CPQ mRNA expression was outstandingly correlated with CD8+ T cells, neutrophils, macrophages and dendritic cell (DC) infiltration. Moreover, CPQ expression was meaningfully associated with the ESTIMATE score and almost all immunomodulatory genes. Conclusions: Low CPQ expression and high methylation are associated with longer OS. CPQ is a promising biomarker for predicting prognosis in patients with GBM.

Boosting CO2 photoreduction by π-π-induced preassembly between a Cu(I) sensitizer and a pyrene-appended Co(II) catalyst.

The design of a highly efficient system for CO2 photoreduction fully based on earth-abundant elements presents a challenge, which may be overcome by installing suitable interactions between photosensitizer and catalyst to expedite the intermolecular electron transfer. Herein, we have designed a pyrene-decorated Cu(I) complex with a rare dual emission behavior, aiming at additional π-interaction with a pyrene-appended Co(II) catalyst for visible light-driven CO2-to-CO conversion. The results of 1H NMR titration, time-resolved fluorescence/absorption spectroscopies, quantum chemical simulations, and photocatalytic experiments clearly demonstrate that the dynamic π-π interaction between sensitizer and catalyst is highly advantageous in photocatalysis by accelerating the intermolecular electron transfer rate up to 6.9 × 105 s-1, thus achieving a notable apparent quantum yield of 19% at 425 nm with near-unity selectivity. While comparable to most earth-abundant molecular systems, this value is over three times of the pyrene-free system (6.0%) and far surpassing the benchmarking Ru(II) tris(bipyridine) (0.3%) and Ir(III) tris(2-phenylpyridine) (1.4%) photosensitizers under parallel conditions.

[Determination of 25-hydroxyvitamin D in serum by pre-column derivatization-stable isotope labeling-ultra performance liquid chromatography-quadrupole electrostatic field orbitrap high-resolution mass spectrometry].

OBJECTIVE: To establish a rapid and accurate method for the determination of 25-hydroxyvitamin D_3(25(OH)D_3) and 25-hydroxyvitamin D_2(25(OH)D_2)in serum by pre-column derivatization with stable isotope labeling and ultra performance liquid chromatography-quadrupole electrostatic field orbitrap high-resolution mass spectrometry, which could be used to diagnose vitamin deficiency and to assess the nutritional status of vitamin D in the population. METHODS: The serum samples with isotopic internal standard were extracted by mixed extraction solvent(ethyl acetate∶hexane = 2∶1, V/V), centrifuged and dried by the nitrogen blowing, and derivatized with 4-phenyl-1, 2, 4-triazoline-3, 5-dione(PTAD). The reaction products were separated on a BEH C_(18) column(2.1 mm×50 mm, 1.7 µm), and eluted with a 0.1% formic acid/water solution-acetonitrile gradient. The mass spectrometry was performed in positive electrospray ionization(ESI~+) and parallel reaction monitoring(PRM) for the detection of the targets, and quantified by isotope internal standard. RESULTS: The limits of detection both for 25(OH)D_3 and 25(OH)D_2 were 0.01 ng/mL and the limits of quantification were 0.03 ng/mL. The concentration series of 25(OH)D_2 ranged from 0.5 to 40.0 ng/mL and the concentration series of 25(OH)D_3 ranged from 2.5 to 200.0 ng/mL. The recoveries(n=5) were 95.7%-101.3% for 25(OH)D_3, and 98.7%-108.6% for 25(OH)D_2, with the relative standard deviations(RSDs) of 0.5%-4.9% and 2.2%-3.4%, respectively. The accuracy of the determination of 25(OH)D_3 and 25(OH)D_2 in Level 2 serum of the 25(OH)D standard reference material NIST SRM 972a was 104.8% and 94.9%, respectively. The M(P25, P75)serum levels of 25(OH)D_3 and 25(OH)D_2 for 116 pregnant women at the first trimester from Beijing were 25.7(20.8, 32.6) ng/mL and 0.8(0.4, 1.1) ng/mL, respectively. CONCLUSION: This method is highly sensitive, qualitatively accurate and suitable for evaluation and monitoring the nutritional status of vitamin D in the population.

A novel zein-selenium complex nanoparticle with controllable size: Quantitative design, physical properties and cytotoxicity in vitro.

In this study, after proposing a method for the preparation of selenium nanoparticles (Se NPs) with stable properties using zein, the physico-chemical properties of zein-Se NPs were tested. The complex structure of zein-Se NPs was deduced by SEM, and the binding mechanism was determined by FT-IR and XPS. The particle size of zein-Se NPs could be regulated from 11.4 ± 0.1 nm to 138.7 ± 0.9 nm under different preparation parameters, the reason for the change in particle size had been speculated. The pH responsiveness and 30-day storage stability of the zein-Se NPs were discussed. The zein-Se NPs still had strong DPPH radical scavenging activity after heat treatment. The zein-Se NPs were cell-friendly and was able to effectively protect cells from H2O2-induced cell-death. This study performed an extensive determination of the underlying physico-chemical properties of zein-Se NPs, we anticipate this approach will open up new possibilities in using natural material to stabilize Se NPs.

Recent trends in degradation strategies of PFOA/PFOS substitutes.

The global elimination and restriction of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), respectively, have urged manufacturers to shift production to their substitutes which still pose threat to the environment with their bioaccumulation, toxicity and migration issues. In this context, efficient technologies and systematic mechanistic studies on the degradation of PFOA/PFOS substitutes are highly desirable. In this review, we summarize the progress in degrading PFOA/PFOS substitutes, including four kinds of mainstream methods. The pros and cons of the present technologies are analyzed, which renders the discussion of future prospects on rational optimizations. Additional discussion is made on the differences in the degradation of various kinds of substitutes, which is compared to the PFOA/PFOS and derives designing principles for more degradable F-containing compounds.

RNF213 inhibits migration in lung adenocarcinoma cell.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, and lung adenocarcinoma (LUAD) accounts for up to 40% of NSCLC. Ring finger protein 213(RNF213) has been demonstrated to suppress several cancers, including glioblastoma and breast cancer. Nonetheless, the role of RNF213 in LUAD has not been investigated. The expression of RNF213 in LUAD tissues was analyzed by western blotting, The Cancer Genome Atlas, Genotype Tissue Expression Project, and Gene Expression Omnibus databases. Prognostic value analysis was performed through the Kaplan-Meier Plotter database. We determined the role of RNF213 in LUAD cells through cell counting kit­8 assay, migration, and invasion assay. The clinical roles of RNF213 were evaluated by immunohistochemical staining assay (IHC) and Kaplan-Meier survival analysis. RNF213 expression was reduced in LUAD, thus affecting the prognosis of LUAD. And RNF213 could suppress the migration and invasion of LUAD cells to prevent tumor development. the expression of RNF213 is positively correlated with the overall survival, providing a novel marker in the prognosis of LUAD patients.

Association of Dietary Patterns with Metabolic Syndrome in Chinese Children and Adolescents Aged 7-17: The China National Nutrition and Health Surveillance of Children and Lactating Mothers in 2016-2017.

This study aims to determine the associations of dietary patterns with metabolic syndrome (MetS) and its components in Chinese children and adolescents aged 7-17 in 2016-2017. Using the data from the China National Nutrition and Health Surveillance of Children and Lactating Mothers in 2016-2017, the sociodemographic information, diet, anthropometric measurements and clinical examinations of subjects were obtained, and a total of 13,071 school-aged children and adolescents were included in this study. The Cook criteria were used to define MetS and its components. Dietary intake was derived from 24-h dietary records for three consecutive days, combined with the weighing method. Factor analysis was used to identify major dietary patterns. The associations of dietary patterns with MetS and its components were examined by logistic regression analysis. Consequently, five distinct dietary patterns were identified by factor analysis, and the relationships between dietary patterns with MetS and its components were observed. After adjusting for covariates, the animal product and vegetable patterns may have a positive association with MetS; the condiment pattern was positively associated with low HDL-C; the fruit and junk food patterns had positive relationships with MetS, abdominal obesity and high TG; the cereals and tubers pattern was positively associated with MetS, abdominal obesity, high TG and low HDL-C; the beans pattern was positively associated with high TG.

Co-facial π-π Interaction Expedites Sensitizer-to-Catalyst Electron Transfer for High-Performance CO2 Photoreduction.

The sunlight-driven reduction of CO2 into carbonaceous fuels can lower the atmospheric CO2 concentration and provide renewable energy simultaneously, attracting scientists to design photocatalytic systems for facilitating this process. Significant progress has been made in designing high-performance photosensitizers and catalysts in this regard, and further improvement can be realized by installing additional interactions between the abovementioned two components, however, the design strategies and mechanistic investigations on such interactions remain challenging. Here, we present the construction of molecular models for intermolecular π-π interactions between the photosensitizer and the catalyst, via the introduction of pyrene groups into both molecular components. The presence, types, and strengths of diverse π-π interactions, as well as their roles in the photocatalytic mechanism, have been examined by 1H NMR titration, fluorescence quenching measurements, transient absorption spectroscopy, and quantum chemical simulations. We have also explored the rare dual emission behavior of the pyrene-appended iridium photosensitizer, of which the excited state can deliver the photo-excited electron to the pyrene-decorated cobalt catalyst at a fast rate of 2.60 × 106 s-1 via co-facial π-π interaction, enabling a remarkable apparent quantum efficiency of 14.3 ± 0.8% at 425 nm and a high selectivity of 98% for the photocatalytic CO2-to-CO conversion. This research demonstrates non-covalent interaction construction as an effective strategy to achieve rapid CO2 photoreduction besides a conventional photosensitizer/catalyst design.

A Preliminary Study on a Form of the 24-h Recall That Balances Survey Cost and Accuracy, Based on the NCI Method.

The 24-h recall (24HR) is a short-term dietary assessment instrument that is widely used in large-scale nutrition surveys. The number of survey days is critical in the accuracy of estimates. The multiple, repeated collection of 24HRs can yield reliable dietary intakes, whereas that is not always feasible due to staffing, equipment, financial, and temporal constraints. The NCI (National Cancer Institute) method was developed to address this limitation by using only within-person variance to calculate usual dietary intake. However, the performance of different forms of 24HRs based on the NCI method remains unclear. The aim of this study was to explore a form of 24HR based on the NCI method that can balance accuracy and survey cost. A total of 595 subjects completed 7 consecutive 24HRs in each season, for a total of 28 24HRs. The averages of the 28 collection days were defined as the reference value to compare the performance of 24HRs for two consecutive days (C2), three consecutive days (C3), two non-consecutive days (NC2), and three non-consecutive days (NC3) for estimating the dietary intakes of Chinese adults. The equivalence test was used to evaluate whether the estimates of scenarios NC2 and NC3 were equivalent. Additionally, the accuracy of a scenario of NC2 which included a weekend was compared to that of a scenario of NC2 which included two weekdays. All results of the 24HRs in each scenario were corrected by the NCI method. Bias/relative bias and mean bias/mean relative bias were used as measures of precision and accuracy, respectively. The results showed that the precision was similar among the four scenarios, while the accuracy relationship varied among the different dietary components. In general, scenario NC3 was the most accurate, followed by scenario NC2, which was close to the former. The form using non-consecutive days was more accurate than that using consecutive days, and the main factor affecting the accuracy of the 24HRs was the continuity between multiple survey days rather than the number of days. The means and major percentiles of energy, nutrients, and frequently consumed food in scenarios NC2 and NC3 were functionally identical. The accuracy of the scenario of NC2 which included a weekend was higher than that of scenario NC2, which consisted of only weekdays. The above results indicated that the adoption of two, non-consecutive 24HRs consisting of a weekend and a weekday to collect dietary data prior to correction by the NCI method, is a feasible approach to balancing survey costs and accuracy in large-scale nutrition surveys.

HOXC11 positively regulates the long non-coding RNA HOTAIR and is associated with poor prognosis in colon adenocarcinoma.

Colorectal cancer ranks third in terms of incidence and second in terms of mortality worldwide. The homeobox transcript antisense intergenic RNA (HOTAIR), which was found to be located on the antisense chain of the homeobox C (HOXC) gene cluster, is a long non-coding RNA involved in multiple types of tumors. The role of HOXC11 in tumors remains unclear. Reverse transcription-quantitative PCR was performed to detect the expression level of HOXC11 in colon adenocarcinoma. Cell proliferation and invasion were assessed. RNase protection assay was used to test the possibility of RNA duplex formation. The increased expression and co-expression trend of HOXC11 and HOTAIR were identified in multiple types of cancer from The Cancer Genome Atlas and the results were validated in 12 colon adenocarcinoma and paired non-tumor tissue samples. The expression of HOXC11 and HOTAIR was found to be associated with poor prognosis in colon adenocarcinoma and kidney renal clear cell carcinoma. Furthermore, HOXC11 was found to positively regulate HOTAIR by RNA duplex formation and promoted the proliferation and invasion of colon adenocarcinoma cells.

Optimal cumulative cisplatin dose during concurrent chemoradiotherapy among children and adolescents with locoregionally advanced nasopharyngeal carcinoma: A real-world data study.

PURPOSE: To identify an optimal cumulative cisplatin dose along with concurrent chemoradiotherapy (CC-CCD) for children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CALANPC) using real-world data. MATERIALS AND METHODS: Using an NPC-specific database at our center, 157 patients younger than 19 years old with non-disseminated CALANPC and receiving neoadjuvant chemotherapy (NAC) plus cisplatin-based concurrent chemoradiotherapy (CCRT) were enrolled. Confounding factors were controlled by conducting propensity score matching analysis. Primary endpoints include disease-free survival (DFS) and distant metastasis-free survival (DMFS). RESULTS: The optimal threshold for CC-CCD with respect to DFS was 160 mg/m2 based on recursive partitioning analyses (RPA). Therefore, a uniform threshold of 160 mg/m2 (≥160 vs. <160 mg/m2) was selected to classify patients between high and low CC-CCD groups for survival analysis. Patients receiving low CC-CCD showed a significant decrease in 5-year DFS (76.6% vs 91.3%; P = 0.006) and DMFS (81.3% vs 93.5%; P = 0.009) compared to those receiving high CC-CCD. Multivariate analyses indicated that high CC-CCD as an favorable prognostic influence for DFS (P = 0.007) and DMFS (P = 0.008). Further matched analysis identified 65 pairs in both high and low CC-CCD groups. In the matched cohort, high CC-CCD was still identified as a favorable factor for prognosis in DFS (HR, 0.23; 95% CI, 0.08-0.70; P = 0.010) and DMFS (HR, 0.23; 95% CI, 0.06-0.82; P = 0.023). CONCLUSION: CC-CCD exerts significant treatment effects and 160 mg/m2 CC-CCD may be adequate to provide antitumor effects for CALANPC receiving NAC plus CCRT.

Decreased expression of nuclear factor 90 correlates with worse outcomes in nasopharyngeal carcinoma.

BACKGROUND: Nuclear factor 90 (NF90), one of the double-stranded RNA binding proteins (DSRBP), is involved in many cellular biological processes, includes cell proliferation, differentiation, angiogenesis, cell cycle and immunity. However, its role in nasopharyngeal carcinoma (NPC), and the significance of expression in clinics, remains unknown. The aim of this study was to uncover the relationship between the NF90 expression by immunohistochemistry (IHC) and clinical outcomes in NPC patients. METHODS: We retrospectively detected the NF90 expression in 216 NPC specimens by IHC. The cutoff value of NF90 was evaluated using receiver operating characteristic (ROC) curve, the prognostic value of NF90 in NPC was evaluated by Kaplan-Meier and cox multifactor statistical model. RESULTS: Elevated expression of NF90 was found in 60.2% (130/216). Positive correlation was found between NF90 expression and clinical stage (P=0.018), T stage (P=0.004), and therapy (P=0.020). Over-expression of NF90 predicted favorable progression-free survival (PFS) (P=0.017) and overall survival (OS) (P<0.001) in NPC. Further analysis suggested that the level of NF90 expression was an independent risk factor in NPC prognosis. CONCLUSIONS: These results demonstrate, for the first time, that decreased expression of NF90 is an independent biomarker of worse prognosis for NPC patients, and is a great potential tool for screening the high-risk population for advanced NPC patients.

Metagenomic next-generation sequencing identified Histoplasma capsulatum in the lung and epiglottis of a Chinese patient: A case report.

Histoplasmosis is an endemic disease mainly occurring in North America and is rare in China. Confirmation of histoplasmosis should be based on a compatible clinical scenario and a positive culture or histopathology. However, there are still many cases that are misdiagnosed or missed, especially in individuals from non-endemic areas. In recent years, metagenomic next-generation sequencing (mNGS) has led to the accurate and timely diagnosis of some rare and complicated infectious diseases. We describe the case of a 27-year-old Chinese man who had chronic progressive pulmonary lesions without any symptoms for more than 1year, until the lesions reached the epiglottis and led to progressive pharyngeal pain. There were no positive results from bronchoalveolar lavage fluid (BALF) and epiglottis tissue cultures, or from epiglottis and lung pathological examinations, but mNGS was able to identify Histoplasma capsulatum in the epiglottis tissues and BALF as the cause of the lesions. The patient was treated successfully with itraconazole.

Retracted: lncRNA IGF2-AS Promotes Cell Proliferation, Migration, and Invasion of Gastric Cancer by Modulating miR-937/EZH2 Axis.

The article entitled, "lncRNA IGF2-AS Promotes Cell Proliferation, Migration, and Invasion of Gastric Cancer by Modulating miR-937/EZH2 Axis," by Zizi Li, Zhanyu Li, Zhijuan Zhong, Jianhui Zhou, Shenhao Huang, Wenying Zhou, and Jianfeng Xu (Cancer Biother Radiopharm epub 25 May 2020; Doi: 10.1089/cbr.2019.3275) is being officially retracted from the literature. The Editor-in-Chief of Cancer Biotherapy and Radiopharmaceuticals (CBR) received an email from the corresponding author of the article, Wenying Zhou, on September 7, 2020, indicating: "…this manuscript should no longer be published [because of] information from our superior and also after discussion with my research team, we want to repeat our experiment and then revise the [manuscript]. Our team has a lot of controversy about these results. In order to ensure the quality of the data and not to mislead readers, we decided to [retract] the manuscript. We will be more rigorous in our further study." The editor requested further information about precisely which data could not be reproduced, to which Dr. Wenying Zhou responded: "…we found that the results of Figure 4B and 4C, Figure 5A and 5B could not be repeated. Our repeated results of Figure 4B and 4C were as follow[s]: compared with miR-NC group, there was no significant decrease of the luciferase activity in miR-937 group when cells co-transfected with EZH2 3'-UTR-WT. Our repeated results of Figure 5A and 5B were as follow[s]: miR-937 inhibited the proliferation of MNK-28 and SGC-7901 cells, but the cell proliferation had no significant change in miR-937+EZH2 group compared with miR-937+pcDNA group. These findings resulted in the uncertainty of the targeted relationship between miR-937 and EZH2. We also repeated these experiments in different environments, but they all contradict the results in the original data. So, the conclusion is very controversial. In a responsible attitude to the readers, we decide to [retract] the manuscript." The authors have extended their apologies to the Editor and to the readers of CBR. Though in the author's original email, the request was made to "withdraw" the paper, CBR has decided to fully retract it due to irreproducible data, as the journal is committed to preserving the scientific literature and the community it serves.

Low expression of ZMYND8 correlates with aggressive features and poor prognosis in nasopharyngeal carcinoma.

PURPOSE: ZMYND8 is closely correlated with cancerous proliferation and invasiveness. However, its prognostic value has not been estimated in a nasopharyngeal carcinoma (NPC). The purpose of this study was to elucidate the status of ZMYND8 expression and its prognostic significance in NPCs. METHODS: The status of ZMYND8 expression was investigated by immunohistochemistry for NPC samples in the study. The cutoff value of ZMYND8 expression was confirmed in NPCs using ROC-curve analysis. Correlations between ZMYND8 expression and clinicopathological variables and patient prognosis were analyzed by various statistical methods. RESULTS: Our study showed that low expression of ZMYND8 strongly correlated with late T stage in NPCs (P<0.05). Kaplan-Meier survival analysis revealed a significant association between low ZMYND8 expression and worse overall survival (P<0.05). Most importantly, Cox regression analysis confirmed ZMYND8 expression in NPC could be an independent prognostic factor. CONCLUSION: Low expression of ZMYND8 could be of importance, due to its displaying more aggressive behavior in NPC. Therefore, ZMYND8 expression might serve as an independent prediction factor in patients with NPCs.

Predictive value of intratumour inflammatory cytokine mRNA levels of hepatocellular carcinoma patients and activation of two distinct pathways govern IL-8 induced epithelial-mesenchymal transition in human hepatic cancer cell lines.

Hepatocellular carcinoma (HCC) is always accompanied by persistent inflammation of liver tissues, which is considered to exert protumourigenic effects by promoting cancer growth, progression, and metastasis. However, the tumour-promoting roles and predictive value of intratumoural inflammatory cytokines remain unclear. In the present study, we used database analysis, clinical pathological studies, and in vitro biological experiments on human hepatic cancer cell lines to assess the prognostic potential of the primary tumour cytokine mRNA levels and underlying mechanisms in HCC. First, we assessed the prognostic value of several cytokines from the TCGA database and found that IL-8 is a unique cytokine that is associated with poor overall survival of HCC patients. Then, we collected 87 HCC tumour and adjacent non-tumour specimens from patients and confirmed that patients with low IL-8 expression exhibited less intrahepatic invasion or distant metastasis, a lower recurrence rate and longer overall survival time compared to patients with high IL-8 expression. Wound healing, transwell, and western blotting assay results showed that IL-8 promotes the migration and invasion of Huh-7 and HepG2 cells, and the underlying mechanism is that IL-8 induces the EMT of HCC cells via the IL-8/ERK1/2/SNAI1 and IL-8/STAT3/TWIST1 signalling pathways. These results provide valuable biological IL-8 information which needs to be further investigated in liver cancer target therapy research. Furthermore, the intratumoural cytokine expression at the mRNA level may provide insight into hepatocarcinoma prognosis.