Phosphate enhanced Cu(II)/peracetic acid process for diclofenac removal: Performance and mechanism.

Since limitedly existing researches suggested Cu(II) had deficiently catalytic ability to PAA, in this work, we tested the oxidation performance of Cu(II)/PAA system on diclofenac (DCF) degradation under neutral conditions. It was found that overwhelming DCF removal could be obtained in Cu(II)/PAA system at pH 7.4 using phosphate buffer solution (PBS) compared to poor loss of DCF without PBS, and the apparent rate constant of DCF removal in PBS/Cu(II)/PAA system was 0.0359 min-1, 6.53 times of that in Cu(II)/PAA system. Organic radicals (i.e., CH3C(O)O• and CH3C(O)OO•) were evidenced as the dominant contributors to DCF destruction in PBS/Cu(II)/PAA system. PBS motivated the reduction of Cu(II) to Cu(I) through chelation effect, and then the activation of PAA by Cu(I) was facilitated. Besides, due to the steric hindrance of Cu(II)-PBS complex (CuHPO4), PAA activation was mediated from non-radical-generating pathway to radical-generating pathway, leading to desirably effective DCF removal by radicals. The transformation of DCF mainly experienced hydroxylation, decarboxylation, formylation and dehydrogenation in PBS/Cu(II)/PAA system. This work proposes the potential of coupling of phosphate and Cu(II) in optimizing PAA activation for organic pollutants elimination.

MicroRNA-644a promotes apoptosis of hepatocellular carcinoma cells by downregulating the expression of heat shock factor 1.

In this study, we investigated the role of microRNA-644a (miR-644a) in the growth and survival of hepatocellular carcinoma (HCC) cells. MiR-644a levels were lower in HCC tissues than in adjacent peri-cancerous tissues (n = 135). MiR-644a expression was inversely correlated with heat shock factor 1 (HSF1) expression, tumour diameter and TNM stage. Moreover, HepG2 and SMMC-7721 cell lines showed lower miR-644a expression than normal L-O2 hepatocytes. MiR-644a overexpression in HepG2 and SMMC-7721 cells increased apoptosis by downregulating HSF1. Dual luciferase reporter assays confirmed the presence of a miR-644a binding site in the 3'-untranslated region (3'-UTR) of HSF1. Xenograft tumours derived from SMMC-7721 cells transfected with a miR-664a mimic showed less growth than tumours derived from untransfected controls. Protein chip analysis revealed that miR-644a-overexpressing SMMC-7721 and HepG2 cells strongly expressed pro-apoptotic BH3-only proteins, such as BID, BAD, BIM, SMAC, Apaf-1 and cleaved caspases-3 and -9. These findings suggest miR-644a promotes apoptosis in HCC cells by inhibiting HSF1.

[Protection Mechanism of Alpinetin on Pulmonary Microvascular Endothelial Cells Injury].

Objective To explore the protection mechanisms about Alpinetin to acute human pulmonary microvascular endothelial cells ( HPMECs ) injury. Methods Different concentration of LPS (0. 01,0. 1 ,1. ,10 mg/L) was applied to the HPMECs to induce acute HPMECs injury. The HPMECs mod- els (n =3) were intervened by Alpinetin(40,80,160,320 mg/L) . Normal HPMECs were selected as control group. The viability of HPMECs was observed,mRNA and protein expression of intercellular cell adhesion molecule-1 (ICAM-1) ,TNF-α,APQ-1 were detected. Results Compared with control group, the protein expression of ICAM-1 , TNF-a were increased, the protein and mRNA expression of APQ-1 and the vi- ability of HPMECs were decreased in model group (P <0. 05). Compared with model group,ICAM-1 and TNF-α protein expressions were significantly inhibited in Alpinetin (80,160 mg/L) group, the mRNA and protein expression of APQ-1 and the viability of HPMECs were significantly increased (P <0. 05, P < 0. 01). Conclusion Alpenitin could protect the HPMECs injury by down-regulated protein expression of ICAM-1, TNF-α and up-regulated the mRNA and protein expression of APQ-1.

HOXA7 plays a critical role in metastasis of liver cancer associated with activation of Snail.

BACKGROUND: Liver cancer is one of the main causes of cancer-related death in human. HOXA7 has been proved to be related with several cancers. METHOD: The expression levels of HOXA7 were examined by Western blot, qRT-PCR or ICH. MTT was used to detect the proliferative rate of liver cancer cells. The invasive abilities were examined by matrigel and transwell assay. The metastatic abilities of liver cancer cells were revealed in BALB/c nude mice. RESULTS: In this report, we revealed that HOXA7 promoted metastasis of HCC patients. First, increased levels of HOXA7 were examined in liver cancer especially in metastatic liver cancer. Moreover, higher expression level of HOXA7 was associated with poorer prognosis of liver cancer patients. Overexpression of HOXA7 significantly enhanced proliferation, migration, invasion in vitro and tumor growth and metastasis in vivo meanwhile silencing HOXA7 significantly inhibited the aboves abilities of liver cancer cells. In this research, we identified that HOXA7 performed its oncogenic characteristics through activating Snail. CONCLUSION: Collectively, we identify the critical role and possible mechanism of HOXA7 in metastasis of liver cancer which suggest that HOXA7 may be a potential therapeutic target of liver cancer patients.

Clinicopathological significance of CXCR4 expression in renal cell carcinoma: a meta-analysis.

BACKGROUND: Emerging evidence indicates that C-X-C chemokine receptor type 4 (CXCR4) is a candidate oncogene in several types of human tumors including renal cell carcinoma (RCC). We conducted a meta-analysis to quantitatively evaluate the association of CXCR4 expression with the incidence of RCC and clinicopathological characteristics. METHODS: We searched PubMed, Embase, and ISI Web of Knowledge to identify studies written in English. Methodological quality of the studies was also evaluated. Odds ratio and hazard ratio were calculated and summarized. RESULTS: Final analysis was performed of 994 RCC patients from 11 eligible studies. We observed that CXCR4 expression was significantly higher in RCC than in normal renal tissues. CXCR4 expression was not found to be associated with sex status or clinical staging. However, CXCR4 expression was clearly associated with Fuhrman grading, metastatic status, and overall survival in RCC patients. CONCLUSIONS: The results of this meta-analysis suggest that CXCR4 expression is associated with an increased risk and worsen survival in RCC patients. The aberrant CXCR4 expression plays an important role in the carcinogenesis and metastasis of RCC.

MicroRNA-155 deficiency attenuates ischemia-reperfusion injury after liver transplantation in mice.

Liver ischemia-reperfusion injury (IRI) is a major cause of morbidity and mortality after resection surgery, liver transplantation, and hemorrhagic and septic shock. Mir-155 is upregulated by a broad range of inflammatory mediators, and it has been demonstrated to be involved in both innate and adaptive immune responses. However, the role of mir-155 in liver IRI has never been investigated. In this study, mir-155 deficiency protected mice from liver IRI, as shown by lower serum alanine aminotransferase (ALT) levels and Suzuki scores. Mir-155 deficiency results in the development of M2 macrophages, which respond to IR-induced innate immune stimulation by producing a regulatory inflammatory response with higher level of IL-10, but lower levels of TNF-α, IL-6, and IL-12p40. Mir-155 deficiency suppresses IL-17 expression, which contributes to the liver IRI development. In our further in vitro study, the results show that the Th17 differentiation is inhibited by SOCS1 overexpression and the promoted M2 macrophage development induced by mir-155 deficiency is abolished by SOCS1 knockdown. In conclusion, mir-155 deficiency attenuates liver IRI through upregulation of SOCS1, and this was associated with promoted M2 macrophage and inhibited Th17 differentiation.

[Retracted] Mammalian STE20­like kinase 1 regulates pancreatic cancer cell survival and migration through Mfn2­mediated mitophagy.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the JC­1 staining images in Fig. 2C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were under consideration for publication at around the same time (a small number of which have been retracted). In addition, the Snail western blot data in Fig. 3E bore a close similarity to certain of the Mfn2 data shown in Fig. 4A. In view of the fact that certain of the contentious data had already apparently been published previously, and owing to a lack of confidence in the presentation of certain of the data in this paper, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 398­404, 2020; DOI: 10.3892/mmr.2020.11098].

Structural Design and Energy and Environmental Applications of Hydrogen-Bonded Organic Frameworks: A Systematic Review.

Hydrogen-bonded organic frameworks (HOFs) are emerging porous materials that show high structural flexibility, mild synthetic conditions, good solution processability, easy healing and regeneration, and good recyclability. Although these properties give them many potential multifunctional applications, their frameworks are unstable due to the presence of only weak and reversible hydrogen bonds. In this work, the development history and synthesis methods of HOFs are reviewed, and categorize their structural design concepts and strategies to improve their stability. More importantly, due to the significant potential of the latest HOF-related research for addressing energy and environmental issues, this work discusses the latest advances in the methods of energy storage and conversion, energy substance generation and isolation, environmental detection and isolation, degradation and transformation, and biological applications. Furthermore, a discussion of the coupling orientation of HOF in the cross-cutting fields of energy and environment is presented for the first time. Finally, current challenges, opportunities, and strategies for the development of HOFs to advance their energy and environmental applications are discussed.

Prognosis and immunotherapy response prediction based on M2 macrophage-related genes in colon cancer.

BACKGROUND: M2 macrophage were revealed to play a crucial role in immune evasion and immunotherapies. This study aims to explore the potential significance of M2 macrophage-related genes in colon adenocarcinoma (COAD) by analysizing the transcriptome data in a comprehensive way. METHODS: We collected RNA-sequencing (RNA-seq) data of COAD from The Cancer Genome Atlas (TCGA) and Gene Expression Ominibus (GEO) databases. We calculated the immune infiltration scores of every sample using CIBERSORT algorithm. Through weighted gene co-expression network analysis (WGCNA), we picked out M2 macrophage-related genes. With these genes we screened out prognosis related genes which were utilized to construct a signature to assess the prognosis of patients. To extend the potential application of the signature, we also calculated the correlations with immune infiltration. Finally, we applied techniques such as quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunoblotting (Western Blotting) to validate the RNF32 gene in cellular in vitro assays. RESULTS: Seven M2 macrophage-related genes signature was constructed, which was an excellent prognostic predictor in two independent groups. The high-risk group showed lower immune infiltration and poorer response to immunotherapies than those of the low-risk group. The cell vitro experiments showed that the expression level of RNF32 was upregulated in colon cancer cell lines compared with normal cell lines. Moreover, we found that RNF32 may promote the proliferation, migration and invasion of cancer cells in vitro by inhibiting apoptosis. CONCLUSION: A novel M2 macrophage-related gene signature affects the prognosis and immune characteristics of colon cancer.

Role of Ubiquitin-specific Proteases in Hepatocellular Carcinoma Pathogenesis.

Signaling pathways in hepatocellular carcinoma are primarily mediated by the phosphorylation and ubiquitination of post-translational proteins. In mammalian cells, ubiquitin-specific proteases (USPs) account for the majority of protein deubiquitination activities. In addition to transcriptional and post-translational regulation, ubiquitination plays an important role in the regulation of key proteins. There is a possibility that altered biological processes may lead to serious human diseases, including cancer. Recent studies have revealed the role of USPs in hepatocellular carcinoma tumorigenesis. The purpose of this review is to summarize the involvement of this class of enzymes in the regulation of cell signaling in hepatocellular carcinoma and the therapeutic development of inhibitors that target USPs, which may lead to novel therapies to treat hepatocellular carcinoma.

Heat induced superfast diclofenac removal in Cu(II)-activated peracetic acid system: Mediation from non-radical to radical pathway.

A Cu(II)/heat coactivated peracetic acid (PAA) system for enhancing diclofenac (DCF) degradation was proposed in this work. The superiority of this synergetic activation strategy for PAA, working reactive species, catalytic mechanism and effects of reaction parameters on DCF elimination in this system were simultaneously investigated. Based on our results, the DCF loss rate in Cu(II)-heat/PAA process at pH 8.0 was about 49.3 and 4.2 times of that in Cu(II)/PAA and heat/PAA processes, respectively. Increasing the reaction temperature to 60 оC not only motivated the conversion of Cu(II) to Cu(I) but also facilitated the one-electron transfer between Cu(I) and PAA, boosting the generation of radicals. Organic radicals (mainly CH3C(O)O• and CH3C(O)OO•) were evidenced to be the core oxidizing substances dominating in the destruction of DCF while hydroxyl radical (•OH) made a minor contribution in this system by electron paramagnetic resonance (EPR) method together with scavenging experiments. This study broads the eyes into enhanced PAA activation initiated by homogenous Cu(II), providing a simple but efficient tool to degrade micropollutants.

Hydroxylamine promoted degradation of organic contaminants using peroxydisulfate activated by Fe-alginate.

To overcome the shortcomings of Fe(Ⅱ)/peroxydisulfate (PDS) system including the limited working pH range and large iron sludge production, a Fe-doped alginate (Fe-Alg) catalyst was prepared and combined with hydroxylamine (HA) to continuously activate PDS for the removal of organic pollutants in neutral condition. Due to the strong reductive capability of HA, it could significantly enhance the catalytic capability of Fe-Alg for PDS. The results of characterization suggested that Fe(Ⅲ)/Fe(Ⅱ) was evenly distributed in Alg through its complexation with carboxyl groups, and the reduction of Fe(Ⅲ) to Fe(Ⅱ) initiated by HA enabled Orange G (OG) to be continuously degraded in the Fe-Alg/HA/PDS system. The results of quenching experiments suggested that SO4∙- and HO• played a dominant role for OG removal in the Fe-Alg/HA/PDS process. The effect of influence factors (e.g. initial pH, HA concentration, Fe-Alg dose and PDS concentration) and water matrix components (i.e. SO42-, NO3-, Cl-, HCO3- and dissolved organic matters (DOM)) on the performance of Fe-Alg/HA/PDS system was systematically investigated. Other refractory organic contaminants, including diclofenac (DCF), sulfamethoxazole (SMX), oxytetracycline (OTC) and bisphenol AF (BPAF) were also efficiently eliminated in Fe-Alg/HA/PDS system, suggesting the feasibility of this system for the treatment of organic pollutants. This work provides a method to optimize Fe(Ⅱ)/PDS system and a novel process applied to degrade refractory pollutants.

[Retracted] Downregulation of δ opioid receptor by RNA interference enhances the sensitivity of BEL/FU drug­resistant human hepatocellular carcinoma cells to 5­FU.

Subsequently to the publication of the above article, and a Corrigendum that was published with the intention of showing corrected data for the flow cytometric plots shown in Fig. 3 (DOI: 10.3892/mmr.2018.9415; published online on August 21, 2018), it was drawn to the Editors' attention by a concerned reader that the ß­actin agarose gel electrophoretic blots shown in Fig. 1A were strikingly similar to data appearing in different form in another article by different authors at a different research institute which had already been published elsewhere prior to this paper's submission to Molecular Medicine Reports. Owing to the fact that the contentious data had already been published else prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 59­66, 2016; DOI: 10.3892/mmr.2015.4511].

UBR7 inhibits HCC tumorigenesis by targeting Keap1/Nrf2/Bach1/HK2 and glycolysis.

BACKGROUND: Glycolysis metabolism is an attractive target for cancer therapy. Reprogramming metabolic pathways could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options. The ubiquitin-proteasome system facilitates the turnover of most intracellular proteins with E3 ligase conferring the target selection and specificity. Ubiquitin protein ligase E3 component N-recognin 7 (UBR7), among the least studied E3 ligases, recognizes its substrate through a plant homeodomain (PHD) finger. Here, we bring into focus on its suppressive role in glycolysis and HCC tumorigenesis, dependent on its E3 ubiquitin ligase activity toward monoubiquitination of histone H2B at lysine 120 (H2BK120ub). METHODS: In this study, we carried out high-throughput RNAi screening to identify epigenetic candidates in regulating lactic acid and investigated its possible roles in HCC progression. RESULTS: UBR7 loss promotes HCC tumorigenesis both in vitro and in vivo. UBR7 inhibits glycolysis by indirectly suppressing HK2 expression, a downstream target of Nrf2/Bach1 axis. Mechanically, UBR7 regulates H2BK120ub to bind to Keap1 promoter through H2BK120ub monoubiquitination, thereby modulating Keap1 expression and downstream Nrf2/Bach1/HK2 signaling. Pharmaceutical and genetic inhibition of glycolytic enzymes attenuate the promoting effect of UBR7 deficiency on tumor growth. In addition, methyltransferase ALKBH5, downregulated in HCC, regulated UBR7 expression in an m6A-dependent manner. CONCLUSIONS: These results collectively establish UBR7 as a critical negative regulator of aerobic glycolysis and HCC tumorigenesis through regulation of the Keap1/Nrf2/Bach1/HK2 axis, providing a potential clinical and therapeutic target for the HCC treatment.

Kinetics and reaction mechanism of photochemical degradation of diclofenac by UV-activated peroxymonosulfate.

Diclofenac (DCF) is a common non-steroidal anti-inflammatory drug, which is frequently detected in different environmental media such as surface water, groundwater, domestic sewage, and sediment. In this study, UV-activated peroxymonosulfate (PMS) was used to degrade DCF by generating active radicals (i.e., SO4˙- and HO˙) with strong oxidizing properties. The effects of PMS dosage, pH, initial DCF concentration and common water constituents on the removal of DCF as well as its degradation mechanism in UV/PMS system were investigated. Compared to UV alone and PMS alone systems, DCF was removed more efficiently in the UV/PMS system at pH 7.0 due to the contribution of SO4˙- and HO˙, and its degradation followed the pseudo-first order kinetic model. As the dosage of PMS or solution pH increased, the degradation efficiency of DCF was gradually enhanced. The highest DCF degradation was obtained at pH 11.0 in this study, because the molar absorption coefficient of PMS increased with increasing pH at 254 nm resulting in generation of more reactive radicals at high pH. Removal efficiency of DCF was decreased significantly with the increase in its initial concentration due to the insufficient concentration of radicals. The presence of HCO3 - and NO3 - could promote the degradation of DCF because of the role of carbonate radicals and extra HO˙ formed, respectively, while NOM inhibited DCF degradation due to its competition with DCF for reactive radicals. No obvious influence on DCF degradation was observed in the UV/PMS system with the addition of Cl- and SO4 2-. The degradation of DCF by UV/PMS in real waters was slightly suppressed compared with its removal in ultrapure water. Seven transformation products were detected using UPLC-QTOF/MS, and the potential degradation mechanism of DCF was thus proposed showing six reaction pathways including hydroxylation, decarboxylation, dechlorination-cyclization, formylation, dehydrogenation and dechlorination-hydrogenation.

Degradation of diclofenac by Fe(II)-activated peracetic acid.

In this study, peracetic acid (PAA) activated by Fe(II) was proposed to remove diclofenac (DCF) in polluted water. It was found that Fe(II)/PAA system could effectively remove DCF at neutral condition, which has a significant advantage over classical Fenton process. According to the result of scavenging experiment, both hydroxyl radical and peroxy radical were considered to be responsible for the degradation of DCF. The influence of several operational parameters including initial pH, Fe(II) dosage, PAA concentration and common water matrix on DCF removal were investigated. 80% DCF was removed at mild condition (pH 6-7) within 60 s, and its removal rate could be enhanced with the increase in Fe(II) dosage and PAA concentration. Presence of HCO3- and natural organic matter (NOM) was proved to have a significantly negative impact on DCF degradation. Four probable degradation pathways of DCF were proposed based on the detected reaction products, including hydroxylation, C-N bond cleavage, decarboxylation and dehydrogenation.

M6A-Mediated Upregulation of LINC00106 Promotes Stemness and Metastasis Properties of Hepatocellular Carcinoma via Sponging Let7f.

Background: Hepatocellular carcinoma (HCC) cells exhibit the stemness property, which makes the patient with HCC prone to tumor recurrence and metastasis. Despite the prominent regulatory role of long non-coding RNAs (lncRNAs) in tumor stemness, the roles and molecular mechanisms of LINC00106 in HCC are poorly understood. Methods: LINC00106, let7f and periostin expression levels in tissue specimens and cell lines were assessed through qRT-PCR and immunohistochemistry (IHC). Various in vivo and in vitro assays, namely sphere/colony formation, proportion of side population cells (SP%), invasion, migration, western blot, and murine xenograft model were employed for assessing the stemness and metastatic properties of HCC cells. Luciferase reporter assays, RNA-seq, RNA pull-down, RNA immunoprecipitation (RIP) were conducted to clarificate the target gene and analyze the underlying mechanisms. Results: LINC00106 was prominently upregulated in tissues and cell lines of HCC. Patients having a high LINC00106 level exhibited a poor outcome. Under in vivo and in vitro conditions, the stemness and metastatic properties of HCC cells were augmented by LINC00106. Additionally, LINC00106 was found to sponge let7f to upregulate periostin, which lead to the activation of periostin-associated PI3K-AKT signaling pathway. Moreover, m6A methylation was found to cause LINC00106 upregulation while maintaining LINC00106 RNA transcript stability. Conclusion: m6A methylation triggers the upregulation of LINC00106, which promotes the stemness and metastasis properties in HCC cells by sponging let7f, thereby resulting in periostin activation. The findings indicate the potential of LINC00106 as a diagnostic marker and therapeutic target for HCC.

Mammalian STE20­like kinase 1 regulates pancreatic cancer cell survival and migration through Mfn2­mediated mitophagy.

Mammalian STE20-like kinase 1 (MST1) plays an important role in pancreatic cancer progression, but its downstream targets are still unknown. In the present study, our results indicated that MST1 expression was significantly downregulated in pancreatic cancer cell lines (PANC­1, BxPC­3 and HPAC) compared with that in the normal ductal epithelial cell line (hTERT­HPNE). Moreover, MST1 overexpression in PANC­1 cells led to increased apoptosis as determined by MTT and TUNEL assays and inhibited cellular migration. Mechanistically, upregulation of MST1 expression caused mitochondrial dysfunction, decreased ATP production, and activation of the mitochondrial­dependent apoptotic pathway via inhibition of mitofusin 2 (Mfn2)­mediated mitophagy, which ultimately resulted in increased cellular apoptosis and decreased cellular migration. Collectively, the present study demonstrated that MST1 may regulate pancreatic cancer PANC­1 cell survival, invasion and migration through Mfn2­mediated mitophagy, laying the foundation for the exploration of novel therapeutic targets for pancreatic cancer.