A Luminescent Cd-MOF Used as a Chemosensor for High-Efficiency Sensing of Fe3+, Cr(IV), Trinitrophenol, and Colchicine.

A Cd-MOF was constructed based on 3,5-bis(4-carboxyphenyl) pyridine under solvothermal conditions. Its structure and phase purity were verified by single-crystal X-ray diffraction. Thereafter, some studies on the morphology, structure, and luminescent properties of the compound were carried out. The compound exhibited a highly sensitive response to Fe3+, Cr(IV), trinitrophenol (TNP), and colchicine based on the fluorescence-quenching mechanism. The possible mechanism of luminescence quenching was discussed in detail.

LncRNA DGUOK-AS1 facilitates non-small cell lung cancer growth and metastasis through increasing TRPM7 stability via m6A modification.

BACKGROUND: N6-methyladenosine (m6A) modification plays key roles in tumor progression. LncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) has been reported as a promoter in tumors, but its role and mechanism in non-small cell lung cancer (NSCLC) development remain uncertain. METHODS: Cell proliferation, migration, invasion and angiogenesis were investigated via CCK-8, colony formation, transwell, and tube formation assays, respectively. The location of DGUOK-AS1 was detected via FISH assay. The interaction relationship among DGUOK-AS1, IGF2BP2 and TRPM7 was confirmed by RIP and MeRIP assays. The effects of DGUOK-AS1 on NSCLC growth and metastasis in vivo were investigated using xenograft and pulmonary metastatic models. RESULTS: DGUOK-AS1 was upregulated in NSCLC. DGUOK-AS1 silencing inhibited NSCLC cell proliferation, migration, invasion and angiogenesis. DGUOK-AS1 was mostly expressed in cytoplasm, and positively regulated IGF2BP2. METTL3/IGF2BP2 axis could increase TRPM7 mRNA stability in m6A-dependent manner. TRPM7 overexpression reversed the inhibitive function of DGUOK-AS1 silencing on NSCLC development. DGUOK-AS1 knockdown suppressed NSCLC cell growth and metastasis in nude mice. CONCLUSION: DGUOK-AS1 silencing restrains NSCLC cell growth and metastasis through decreasing TRPM7 stability via regulation of the METTL3/IGF2BP2-mediated m6A modification.

A Water-Stable Zn-MOF Used as Multiresponsive Luminescent Probe for Sensing Fe3+/Cu2+, Trinitrophenol and Colchicine in Aqueous Medium.

A water-stable Zn-MOF was constructed based on H2PBA and 1, 10-phenanthroline under solvothermal conditions. The compound exhibited a 3D (2,3,8)-connected (43)2(46.66.815.12)(8) topology framework. The crystal structure and phase purity of the compound was verified by single crystal X-ray diffraction. Subsequently, some studies on the morphology, structure, and luminescent properties were carried out. The results showed that this compound could be used as a versatile chemosensor for Fe3+/Cu2+, trinitrophenol and colchicine via a luminescence quenching effect in an aqueous medium.

IL-35 enhances angiogenic effects of small extracellular vesicles in breast cancer.

As an indispensable process for breast cancer metastasis, tumour angiogenesis requires a tight interaction between cancer cells and endothelial cells in tumour microenvironment. Here, we explored the participation of small extracellular vesicles (sEVs) derived from breast cancer cells in modulating angiogenesis and investigated the effect of IL-35 in facilitating this process. Firstly, we characterized breast cancer cells-derived sEVs untreated or treated with IL-35 and visualized the internalization of these sEVs by human umbilical vein endothelial cells (HUVECs). Breast cancer cells-derived sEVs promoted endothelial cell proliferation through facilitating cell cycle progression and enhanced capillary-like structures formation and microvessel formation. Subsequent results proved that IL-35 further reinforced the angiogenic effect induced by breast cancer cells-derived sEVs. Moreover, sEVs from breast cancer cells significantly enhanced tumour growth and microvessel density in breast tumour-bearing mice model. Microarray analysis showed that IL-35 might alter the mRNA profiles of sEVs and activate the Ras/Raf/MEK/ERK signalling pathway. These findings demonstrated that IL-35 indirectly promoted angiogenesis in breast cancer through regulating the content of breast cancer cells-derived sEVs, which could be internalized by HUVECs.

Role of extracellular polymeric substances on the behavior and toxicity of silver nanoparticles and ions to green algae Chlorella vulgaris.

The effect of extracellular polymeric substances (EPS), vital organic matters and nutrient elements in the natural environment, on the behavior and toxicology of silver nanoparticles (AgNPs) and ions remains ambiguous. In this study, the role of EPS on the toxicity of AgNPs and dissolved silver ions (from AgNO3) to a green algae Chlorella vulgaris was investigated. After the removal of EPS, algae accumulated more silver, about 7.41- and 1.25-fold of those in the algae with EPS for AgNPs and AgNO3 treatments, respectively. The large amount of accumulated silver was bound to the algal cell surface for AgNPs treatment and was internalized in the algae for AgNO3 treatment, irrespective of the presence of EPS in algae. After exposure to AgNPs, the ruffles in the surfaces of algal cells were filled by AgNPs, and almost invisible. FTIR showed that for both AgNPs and AgNO3, the aldehyde groups on the cell surface were oxidized to carboxyl groups by silver ions, irrespective of the presence of EPS in algal cells, indicating that silver ions were released from the oxidization of AgNPs and reacted with algal cells. The content of chlorophyll showed that AgNPs depressed algal growth more remarkably than did AgNO3, independent of the presence of EPS in algae, suggesting that AgNPs had greater toxic effects on algae than did silver ions. The findings suggest that the barrier effect of EPS gave nanoparticles an extraordinary edge over ions, but EPS had no discerning effect on the interaction of algal cells with the silver ions released from AgNPs and AgNO3, and also on the effect of AgNPs and AgNO3 on algal growth.

Correlations of Galectin-3 Gene Polymorphisms with Risk and Prognosis of Cervical Cancer in Chinese Populations: A Case-Control Study.

BACKGROUND: This study explores correlations of galectin-3 gene polymorphisms (rs4644, rs4652, and rs11125) with cervical cancer risk and prognosis in Chinese populations. METHODS: A total of 126 patients with cervical cancer were selected to form the case group, and 102 healthy people were selected for the control group following a physical examination. 3 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The distribution frequencies of the CC+CA genotype of rs4652 and the AT+TT genotype of rs11125 in the case group were remarkably higher than those in the control group. rs4644 only had correlations with tumor diameter, while rs4652 and rs11125 had correlations with tumor diameter, FIGO staging, differentiation grades, clinical staging, lymph node metastasis (LNM), and treatment modality. The 5-years survival rate of patients with CC+CA of rs4652 was lower but the recurrence rate was higher compared to AA type patients. In contrast, AA type patients with rs11125 had a higher 5-year survival rate but a lower recurrence rate than those of AT+TT type. CC+CA genotype of rs4652, AT+TT genotype of rs11125, and treatment modality were independent factors related to overall survival and disease-free survival, and LNM was an independent factor related to OS. CONCLUSION: Our findings provide evidence that allele C of rs4652 and allele T of rs11125 in the galectin-3 gene may be risk factors for cervical cancer.

The Mechanism of Proinflammatory HDL Generation in Sickle Cell Disease Is Linked to Cell-Free Hemoglobin via Haptoglobin.

In sickle cell disease (SCD), the inflammatory properties of high-density lipoprotein (HDL) can be changed by cell-free hemoglobin (Hb), which is released into the blood during hemolysis. Hb in the plasma of SCD patients or mice can bind with HDL specifically inducing an inflammatory reaction. In our study, we found increased amounts of inflammatory factor proteins in the chronic oxidative state of SCD with higher levels of Hb, haptoglobin (Hp) and hemopexin (Hx) in the apolipoprotein A-I (ApoA-1) particles of HDL and the role of HDL is changed from being anti-inflammatory to proinflammatory. Our results also suggest Hp and Hx, the scavengers of Hb in HDL, are positively associated with inflammatory levels in SCD patients. HDL retained its inflammatory inhibition role in Hp-/- mice, with less Hb accumulation. Hx may further prevent inflammatory reaction because its level will be even higher when lack of Hx. We therefore demonstrated that Hp is indispensable during the process whereby Hb associates with HDL and plays a clear proinflammatory role. Therefore, it is essential to break the binding between Hb and Hp for treatment. The dissociation of Hb/Hp/Hx complexes may also play an important role in the study of other inflammatory angiogenesis-related diseases.

Expression of P21-activated kinase 1 and cell division control protein 42 homolog correlates with clinicopathological features and prognosis in cervical carcinoma.

AIM: This study investigated P21-activated kinase 1 (PAK1) and cell division control protein 42 homolog (CDC42) expression and their correlation with clinicopathological features and prognosis in cervical carcinoma. METHODS: Cervical carcinoma (n = 55), cervical intraepithelial neoplasias (CIN, n = 93), and normal cervix (n = 26) tissues were sampled. PAK1 and CDC42 expressions were determined using real-time quantitative polymerase chain reaction, Western blot and immunohistochemistry. Correlation analysis of PAK1 and CDC42 expression was performed using a Pearson correlation test. Survival rate was calculated using the Kaplan-Meier method. Independent prognostic factors were analyzed by Cox proportional hazard model. RESULTS: PAK1 and CDC42 expression were positively correlated in all tissues. PAK1 and CDC42 expression in cervical carcinoma tissues were higher than those in normal tissues. PAK1 and CDC42 protein expression in normal cervix, CINI, CINII, CINIII and cervical carcinoma tissues showed a gradually increasing trend. PAK1 and CDC42 expression were correlated with lymph node metastasis, the depth of tumor invasion, the degree of tumor differentiation, histological type and lymphovascular space invasion (LVSI; all P < 0.05). Cox regression analysis showed that the degree of tumor differentiation, PAK1 protein expression, histological type and LVSI are independent risk factors for prognosis of cervical carcinoma. CONCLUSION: High PAK1 and CDC42 expressions are closely related to the clinicopathological features and poor prognosis of cervical carcinoma, serving as unfavorable prognostic factors.

ß-Arrestin 2 Promotes Hepatocyte Apoptosis by Inhibiting Akt Protein.

Recent studies reveal that multifunctional protein ß-arrestin 2 (Arrb2) modulates cell apoptosis. Survival and various aspects of liver injury were investigated in WT and Arrb2 KO mice after bile duct ligation (BDL). We found that deficiency of Arrb2 enhances survival and attenuates hepatic injury and fibrosis. Following BDL, Arrb2-deficient mice as compared with WT controls displayed a significant reduction of hepatocyte apoptosis as demonstrated by the TUNEL assay. Following BDL, the levels of phospho-Akt and phospho-glycogen synthase kinase 3ß (GSK3ß) in the livers were significantly increased in Arrb2 KO compared with WT mice, although p-p38 increased in WT but not in Arrb2-deficient mice. Inhibition of GSK3ß following BDL decreases hepatic apoptosis and decreased p-p38 in WT mice but not in Arrb2 KO mice. Activation of Fas receptor with Jo2 reduces phospho-Akt and increases apoptosis in WT cells and WT mice but not in Arrb2-deficient cells and Arrb2-deficient mice. Consistent with direct interaction of Arrb2 with and regulating Akt phosphorylation, the expression of a full-length or N terminus but not the C terminus of Arrb2 reduces Akt phosphorylation and coimmunoprecipates with Akt. These results reveal that the protective effect of deficiency of Arrb2 is due to loss of negative regulation of Akt due to BDL and decreased downstream GSK3ß and p38 MAPK signaling pathways.

Chronic morphine-induced microRNA-124 promotes microglial immunosuppression by modulating P65 and TRAF6.

Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects including immunosuppression. However, the mechanisms are unclear. TLRs and acetylcholine are widely expressed in the immune and nervous systems, and play critical roles in immune responses. In this article, we show that morphine suppresses the innate immunity in microglia and bone marrow-derived macrophages through differential regulation of TLRs and acetylcholinesterase. Either morphine or inhibition of acetylcholine significantly promotes upregulation of microRNA-124 (miR-124) in microglia, bone marrow-derived macrophages, and the mouse brain, where miR-124 mediates morphine inhibition of the innate immunity by directly targeting a subunit of NF-κB p65 and TNFR-associated factor 6 (TRAF6). Furthermore, transcription factors AP-1 and CREB inhibited miR-124, whereas p65 bound directly to promoters of miR-124, thereby enhancing miR-124 transcription. Moreover, acute morphine treatment transiently upregulated the expression of p65 and phospho-p65 in both nucleus and cytoplasm priming the expression of miR-124, whereas long exposure of morphine maintained miR-124 expression, which inhibited p65- and TRAF6-dependent TLR signaling. These data suggest that modulation of miRs is capable of preventing opioid-induced damage to microglia.

ß-arrestin2/miR-155/GSK3ß regulates transition of 5'-azacytizine-induced Sca-1-positive cells to cardiomyocytes.

Stem-cell antigen 1-positive (Sca-1+) cardiac stem cells (CSCs), a vital kind of CSCs in humans, promote cardiac repair in vivo and can differentiate to cardiomyocytes with 5'-azacytizine treatment in vitro. However, the underlying molecular mechanisms are unknown. ß-arrestin2 is an important scaffold protein and highly expressed in the heart. To explore the function of ß-arrestin2 in Sca-1+ CSC differentiation, we used ß-arrestin2-knockout mice and overexpression strategies. Real-time PCR revealed that ß-arrestin2 promoted 5'-azacytizine-induced Sca-1+ CSC differentiation in vitro. Because the microRNA 155 (miR-155) may regulate ß-arrestin2 expression, we detected its role and relationship with ß-arrestin2 and glycogen synthase kinase 3 (GSK3ß), another probable target of miR-155. Real-time PCR revealed that miR-155, inhibited by ß-arrestin2, impaired 5'-azacytizine-induced Sca-1+ CSC differentiation. On luciferase report assay, miR-155 could inhibit the activity of ß-arrestin2 and GSK3ß, which suggests a loop pathway between miR-155 and ß-arrestin2. Furthermore, ß-arrestin2-knockout inhibited the activity of GSK3ß. Akt, the upstream inhibitor of GSK3ß, was inhibited in ß-arrestin2-Knockout mice, so the activity of GSK3ß was regulated by ß-arrestin2 not Akt. We transplanted Sca-1+ CSCs from ß-arrestin2-knockout mice to mice with myocardial infarction and found similar protective functions as in wild-type mice but impaired arterial elastance. Furthermore, low level of ß-arrestin2 agreed with decreased phosphorylation of AKT and increased phophorylation of GSK3ß, similar to in vitro findings. The ß-arrestin2/miR-155/GSK3ß pathway may be a new mechanism with implications for treatment of heart disease.

FoxM1 is overexpressed in Helicobacter pylori-induced gastric carcinogenesis and is negatively regulated by miR-370.

UNLABELLED: Helicobacter pylori (H. pylori) infections are strongly implicated in human gastric mucosa-associated diseases. Forkhead box M1 (FoxM1), a key positive regulator of cell proliferation, is overexpressed in gastric cancer. MicroRNAs are important post-transcriptional regulators of gene expression. In this study, the effects of H. pylori infection on FoxM1 expression and possible mechanisms of carcinogenesis were explored. The expression of FoxM1 was gradually increased in human gastric specimens from inflammation to cancer. FoxM1 upregulation was time- and concentration-dependent in gastric epithelial-derived cell lines infected with H. pylori. CagA, a key virulence factor of H. pylori, was associated with increased FoxM1 expression. H. pylori and CagA inhibited the expression of p27(Kip1) (CDKN1B) and promoted cell proliferation by upregulating FoxM1. The expression of miR-370 was decreased in human gastritis and gastric cancer. FoxM1 was directly downregulated by miR-370 in gastric cell lines. H. pylori and CagA inhibited miR-370 expression, which led to overexpression of FoxM1 and cell proliferation. Furthermore, the overexpression of FoxM1 and reduced expression of miR-370 was confirmed in H. pylori-infected C57BL/6J mice. H. pylori infection and CagA upregulated FoxM1 expression, dependent on miR-370, altered the expression of p27(Kip1), and promoted proliferation in gastric cells. IMPLICATIONS: These findings delineate the mechanisms governing FoxM1 regulation and the role of H. pylori in the process of gastric carcinogenesis.

Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with poor clinical outcome. Identification and development of new markers could be beneficial for the diagnosis and prognosis of GBM patients. Deregulation of microRNAs (miRNAs or miRs) is involved in GBM. Therefore, we attempted to identify and develop specific miRNAs as prognostic and predictive markers for GBM patient survival. METHODS: Expression profiles of miRNAs and genes and the corresponding clinical information of 480 GBM samples from The Cancer Genome Atlas (TCGA) dataset were downloaded and interested miRNAs were identified. Patients' overall survival (OS) and progression-free survival (PFS) associated with interested miRNAs and miRNA-interactions were performed by Kaplan-Meier survival analysis. The impacts of miRNA expressions and miRNA-interactions on survival were evaluated by Cox proportional hazard regression model. Biological processes and network of putative and validated targets of miRNAs were analyzed by bioinformatics. RESULTS: In this study, 6 interested miRNAs were identified. Survival analysis showed that high levels of miR-326/miR-130a and low levels of miR-323/miR-329/miR-155/miR-210 were significantly associated with long OS of GBM patients, and also showed that high miR-326/miR-130a and low miR-155/miR-210 were related with extended PFS. Moreover, miRNA-323 and miRNA-329 were found to be increased in patients with no-recurrence or long time to progression (TTP). More notably, our analysis revealed miRNA-interactions were more specific and accurate to discriminate and predict OS and PFS. This interaction stratified OS and PFS related with different miRNA levels more detailed, and could obtain longer span of mean survival in comparison to that of one single miRNA. Moreover, miR-326, miR-130a, miR-155, miR-210 and 4 miRNA-interactions were confirmed for the first time as independent predictors for survival by Cox regression model together with clinicopathological factors: Age, Gender and Recurrence. Plus, the availability and rationality of the miRNA-interaction as predictors for survival were further supported by analysis of network, biological processes, KEGG pathway and correlation analysis with gene markers. CONCLUSIONS: Our results demonstrates that miR-326, miR-130a, miR-155, miR-210 and the 4 miRNA-interactions could serve as prognostic and predictive markers for survival of GBM patients, suggesting a potential application in improvement of prognostic tools and treatments.

Penta-aqua-bis[4-(2-hydroxy-benzyl-idene-amino)benzene-sulfonato]lead(II).

In the structure of the title compound, [Pb(C(13)H(10)NO(4)S)(2)(H(2)O)(5)], two S-O bonds and one C-N bond have lengths of 1.421 (9), 1.425 (8) and 1.268 (11) Å, respectively, which suggests they are double bonds. Mol-ecules form a two-dimensional layered structure via O-H⋯O and O-H⋯N inter-actions. The Pb atom adopts distorted cubo-octahedral coordination.

N-(1-Naphth-yl)acetoacetamide.

The title compound, C(14)H(13)NO(2), exists in the keto form. An N-H⋯O hydrogen bond helps to establish the packing.

{2,2'-[4-Methyl-4-aza-heptane-1,7-diylbis(nitrilo-methyl-idyne)]diphenolato}zinc(II).

In the title compound, [Zn(C(21)H(25)N(3)O(2))], the Zn(II) atom is five-coordinate from three N donor atoms and two O donor atoms of the dianion ligand in a distorted trigonal-bipyramidal arrangement. Three methyl-ene groups of the ligand are disordered over two orientations in a 0.555 (6):0.445 (6) ratio.

Bis(2-amino-pyrimidine-κN)diaqua-dinitrato-κO;κO,O'-cadmium(II) monohydrate.

In the title compound, [Cd(NO(3))(2)(C(4)H(5)N(3))(2)(H(2)O)(2)]·H(2)O, the Cd atom is seven-coordinated by two 2-amino-pyrimidine mol-ecules, two water mol-ecules, one bidentate nitrate anion and one monodentate nitrate anion. A network of N-H⋯O, N-H⋯N and O-H⋯O hydrogen bonds helps to consolidate the crystal structure.

N'-(3-Ethoxy-2-hydroxybenzylidene)-benzenesulfonohydrazide.

There are two mol-ecules in the asymmetric unit of the title compound, C(15)H(16)N(2)O(4)S, both of which are stabilized by an intra-molecular O-H⋯N hydrogen bond. Inter-molecular N-H⋯O hydrogen bonds lead to [101] chains of mol-ecules in the crystal structure.

1-Hydroxymethyl-3,12-dioxa-14-aza-tetracyclo[9.2.1.0.0]tetradecane.

In the title fused-ring compound, C(12)H(13)NO(3), the two five-membered C(3)NO rings both approximate to envelope conformations with C atoms in the flap positions. The OH group of the pendant CH(2)OH unit is disordered over two positions in a 0.528 (5):0.472 (5) ratio. One of the OH groups participates in an O-H⋯N hydrogen bond, generating centrosymmetric dimers in the crystal structure.

Hexaaqua-cobalt(II) bis-[4-(2-hydroxy-benzyl-ideneamino)-benzene-sulfonate].

In the cation of the title compound, [Co(H(2)O)(6)](C(13)H(10)NO(4)S)(2), the Co atom lies on a centre of symmetry and its coordination geometry is octahedral. The crystal structure is stabilized by water-anion O-H⋯O hydrogen bonds. An intra-molecular O-H⋯N hydrogen bond occurs in the anion.