Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway.

BACKGROUND: Heterogeneous ribonucleoprotein A1 (hnRNPA1) has been reported to enhance the Warburg effect and promote colon cancer (CC) cell proliferation, but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated. AIM: To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway. METHODS: Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b. The relationship between the expression values and the clinicopathological features of the patients was investigated. Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction, while differences in protein expression were analyzed using western blot. Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays, and cell cycle and apoptosis were detected using flow cytometric assays. The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay. The Warburg effect was evaluated by glucose uptake and lactic acid production assays. RESULTS: The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls (P < 0.05). Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC, including stage I, II-III, and IV. Furthermore, the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification. HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway, thereby promoting proliferation of HCT116 and SW620 cells. However, the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b, effectively blocking the Warburg effect. CONCLUSION: These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

A water stable Eu(III)-organic framework as a recyclable multi-responsive luminescent sensor for efficient detection of p-aminophenol in simulated urine, and MnVII and CrVI anions in aqueous solutions.

A novel 3D Eu(iii) metal-organic framework (Eu-MOF-1) formulated as [Eu(L)(H2O)(DMA)] (L = 2-(2-nitro-4-carboxylphenyl)terephthalic acid) has been successfully synthesized under solvothermal conditions and characterized by structural analyses. Eu-MOF-1 displays a new 3D framework containing EuIII ions, ligand L, and coordinated DMA molecules and water molecules. The fluorescence investigations indicate that Eu-MOF-1 emits bright red luminescence, and shows relatively high water stability and outstanding chemical stability under a relatively wide range of pH conditions. It is noteworthy that Eu-MOF-1 can quantitatively detect p-aminophenol (PAP) which is a metabolite of phenylamine in human urine. More significantly, Eu-MOF-1 is the first reported multi-responsive luminescent sensor for detecting the biomarker PAP, and MnVII and CrVI anions with high selectivity, sensitivity, recyclability and relatively low detection limits in aqueous solutions. Furthermore, the possible sensing mechanisms of Eu-MOF-1 for selective sensing have also been explored in detail. Eu-MOF-1 could be an ideal candidate as a multi-responsive luminescent sensor in biological and environmental areas.

Water-stable Cd(ii)/Zn(ii) coordination polymers as recyclable luminescent sensors for detecting hippuric acid in simulated urine for indexing toluene exposure with high selectivity, sensitivity and fast response.

Three novel Cd(ii)/Zn(ii) coordination polymers (CPs), namely [Cd(L)(BPDC)0.5H2O]·0.5H2O (1), [Zn2(L)2(BPDC)]·2H2O (2) and [Cd2(L)(BTC)H2O]·3H2O (3) (L = 4-(tetrazol-5-yl)phenyl-4,2':6',4''-terpyridine, H2BPDC = 4,4'-biphenyldicarboxylic acid, and H3BTC = 1,3,5-benzenetricarboxylic acid), have been successfully synthesized and characterized. CP 1 and CP 2 display new two-dimensional double-layered honeycomb frameworks containing uncoordinated nitrogen atoms from pyridine and tetrazole rings, which can easily form hydrogen bonds with various analytes. CP 3 exhibits a 3D framework also with uncoordinated nitrogen atoms from pyridine and tetrazole rings. The fluorescence explorations indicate that CPs 1-3 exhibit strong blue luminescence and excellent chemical stability under a relatively wide range of pH conditions. It is worth noting that CPs 1-3 can quantitatively detect hippuric acid (HA), which is a metabolite of toluene in human urine, with high selectivity, sensitivity, fast response and relatively low detection limits. Moreover, the sensing mechanism of CPs 1-3 for HA can mainly be ascribed to fluorescence resonance energy transfer (FRET). CPs 1-3 could be ideal candidates as HA sensors in human urine samples for practical applications. Notably, to the best of our knowledge, we report for the first time Cd(ii)/Zn(ii)-based luminescent sensors for detecting HA in simulated urine.

3D LnIII-MOFs: slow magnetic relaxation and highly sensitive luminescence detection of Fe3+ and ketones.

Five new 3D isostructural lanthanide metal organic frameworks (Ln-MOFs), [Ln(HL)1.5(H2O)(DMF)]·2H2O (Ln = GdIII (1), SmIII (2), DyIII (3), EuIII (4) and TbIII (5), H3L = 5-(3',5'-dicarboxylphenyl) nicotinic acid) were synthesized by solvothermal methods and studied by structural analyses, magnetic analyses and luminescence sensing. Crystallographic studies revealed that these compounds are 3D frameworks in which the LnIII-COO chains with alternating four and two carboxylate bridges are interlinked by the organic ligands L, and contain microporous channels with accessible Lewis-base sites, coordinated water molecules and uncoordinated carboxyl groups, which are easy to combine and recognise various analytes. Magnetic studies demonstrated that the carboxylate bridges transmit interchain dominant ferromagnetic interactions in Gd-MOF (1) and Dy-MOF (3), while the decrease of the χT value in Sm-MOF (2) is due to the thermal depopulation effect of the excited levels. Furthermore, Dy-MOF (3) also shows slow magnetic relaxation behaviour under a zero dc field. The luminescence selective sensing experiments showed that Eu-MOF (4) and Tb-MOF (5) can act as recyclable sensors towards Fe3+ ions in water and the simulated biological fluids, and towards ketones in a water system with high sensitivity, selectivity and relatively low detection limits.

Blockade of presynaptic 4-aminopyridine-sensitive potassium channels increases initial neurotransmitter release probability, reinstates synaptic transmission altered by GABAB receptor activation in rat midbrain periaqueductal gray.

The activation of γ-aminobutyric acid receptor subtype B (GABAB) receptors in the midbrain ventrolateral periaqueductal gray (vlPAG) induces both postsynaptic and presynaptic inhibition. Whereas the postsynaptic inhibition is mediated by G protein-coupled inwardly rectifying K channels, the presynaptic inhibition of neurotransmitter release is primarily mediated by voltage-gated calcium channels. Using whole-cell recordings from acute rat PAG slices, we report here that the bath application of 4-aminopyridine, a voltage-gated K channel blocker, increases the initial GABA and glutamate release probability (P) and reinstates P depressed by presynaptic GABAB receptor activation at inhibitory and excitatory synapses, respectively. However, Ba, which blocks G protein-coupled inwardly rectifying K channels, does not produce similar effects. Our data suggest that the blockade of presynaptic 4-aminopyridine-sensitive K channels in vlPAG facilitates neurotransmitter release and reinstates synaptic transmission that has been altered by presynaptic GABAB receptor activation. Because vlPAG is involved in the descending pain control system, the present results may have potential therapeutic applications.

[Expression of key enzyme genes and content of saikosaponin in saikosaponin biosynthesis under drought stress in Bupleurum chinense].

To research the expression of key enzymes in saikosaponin biosynthesis and the content of saikosaponin under the drought stress, the study focused on the gene-level and the end product responses to environmental change. Taking the five months of Bupleurum chinense as research materials, the contents of saikosaponin A and saikosaponin D under different stress levels were measured by HPLC. The drought was simulated by poly ethylene glycol. The real-time fluorescence quantitative PCR was used to analyze the expression of four key enzymes genes HMGR, IPPI, FPS, ß-AS and the expression of ß-tubulin was set as a reference gene. The results showed that drought stress significantly improved the content of saikosaponin. The contents of SSa and SSd were highest researching 0.648% and 0.781%, respectively when the concentration of PEG was 10%. Meanwhile, the results reflected that the expression of four key enzymes had risen differently and FPS, ß-AS raised significantly(P<0.01). In addition, the results of correlation analysis showed that there was a significant positive correlation between the expression of the four key enzymes genes and the content of saikosaponin. In a word, the contents of secondary metabolites were regulated by the expression of key enzymes genes under the drought stress in B. chinense.

Chinese Internet Searches Provide Inaccurate and Misleading Information to Epilepsy Patients.

BACKGROUND: Most patients with epilepsy want to learn as much as possible about the disease, and many have turned to the internet for information. Patients are likely to use information obtained from the internet to control their epilepsy, but little is known about the accuracy of this information. In this survey, we have assessed the feasibility and usability of internet-based interventions for the treatment of epilepsy. METHODS: Data were collected from an internet search. Different search terms were used to obtain general information on epilepsy together with information about medication, types of epilepsy, treatment, women's health, and other information. The accuracy of the information was evaluated by a group of experts. RESULTS: A total of 1320 web pages were assessed. The majority were websites related to health. A large number (80.2%) of web pages contained content related to the search term. A significant number of web pages 450/1058 (42.5%) claimed to provide information from a credible source; however, only 206/1058 (19.5%) of the information was accurate and complete; 326/1058 (30.8%) was accurate but incomplete; 328/1058 (31.0%) was correct but nonstandard, and 198/1058 (18.8%) was inaccurate. The authenticity of the information was not significantly different between the two search engines (χ2 = 0.009, P = 0.924). No significant difference was observed in the information obtained from a specialist or nonspecialist source (χ2 = 7.538, P = 0.057). There was also no correlation between the quality of the information and the priority (χ2 = 6.880, P = 0.076). CONCLUSIONS: Searching for information about epilepsy on the internet is convenient, but the information provided is not reliable. Too much information is inaccurate or for advertisement purposes, and it is difficult for patients to find the useful information. Turning to the internet for medical knowledge may be harmful. Physicians should be aware that their patients may search for information on the internet and guide them to safe, reputable websites.

Clinicopathological study of sporadic Burkitt lymphoma in children.

BACKGROUND: Non-Hodgkin lymphoma is the fourth most common malignant tumors in children, Burkitt lymphoma (BL) accounts for 30-50% of all pediatric lymphomas. The aim of this study was to investigate the clinicopathologic features, immunophenotype, Epstein-Barr virus (EBV) infection and c-myc gene rearrangement of sporadic BL in children. METHODS: Ninety-two cases of pediatric BL were retrospectively analyzed for clinical features, immunohistochemistry, EBV-encoded RNA (EBER) status by in situ hybridization and c-myc gene rearrangement by fluorescence in situ hybridization. RESULTS: In the 92 cases, male is predominant in sex distribution (M: F = 3.38:1). The average age at diagnosis was 4.97 years. Polypoid BL showed a lower clinical stage (P = 0.002), and advanced clinical stage and low serum albumin level at diagnosis were associated with poor outcome (P = 0.024 and 0.053, respectively). The positive expression of CDl0, B-cell lymphoma-6, MUMl and EBER were 95.7% (88 cases), 92.4% (85 cases), 22.8% (21 cases), 41.3% (38 cases), respectively. The expression of MUM1 were not associated with EBV infection status (P = 1.000). c-myc gene rearrangement was detected in 94.6% (87/92). Clinical treatment information for 54 cases was collected, 21 patients died of tumor after surgery alone, 33 patients received surgery and chemotherapy, and of which six patients died shortly afterwords (MUM1 positive expression in 3 cases, P = 0.076). CONCLUSIONS: The anatomical location, growth pattern and serum albumin level of BL were associated with biological behavior. MUM1 may be a potential adverse prognostic marker, and not associated with EBV infection status.

[Effect of Eu ions on the Ag nanoparticles precipitation and their optical properties in borate glasses].

Eu-Ag co-doped borate glasses were prepared by the high temperature solid method in the present work. Absorption and emission spectra were employed to investigate the precipitation of Ag nanoparticles, which is influenced by the network form B2O3 and the co-doped Eu ions. It was found in the absorption spectra of Eu-Ag co-doped sample that a broad band centered at about 410 nm emerged and their intensity decreased with the increase in the BZ 03 concentration. Meanwhile, under the excitation of 340 nm, a broad emission band was observed in the wavelength range of 350-600 nm, which belongs to the blue-green light of Ag aggregates. The intensity of the Ag aggregates presented an increasing tendency with the increase in the B2O3 contents. The weak characteristic emission of Ag aggregates and Eu3+ was observed respectively in their singly doped samples. It is concluded that both their emissions get significant enhancement when Eu ions and Ag ions are used for co-doping the sample. In addition, the increased absorption of Ag nanoparticles was detected with the increase in the Eu ions concentration. Herein, the mechanism behind Eu3+ contribution to the precipitation of Ag nanoparticles is discussed in detail. The luminescence properties of borate glasses can be controlled by the microstructure of the borate glasses. Therefore, the white emission can be realized by the adjustment of glass structure and Eu ions concentration, owing to the red light from Eu3+ : (5)D0-->(7)Fj electronic transition and the blue-green light form the broad emission of Ag aggregates. The borate glasses are expected to be the candidates for the light-emission diode (LED) luminescent materials.

GABAB receptors resist acute desensitization in both postsynaptic and presynaptic compartments of periaqueductal gray neurons.

The ventrolateral midbrain periaqueductal gray (PAG) neurons have been intensively studied because of their pivotal role in the descending pain modulation system. Activation of GABAB receptors, one type of inhibitory G-protein-coupled receptors (GPCRs), in PAG neurons results in both presynaptic and postsynaptic inhibition. Acute desensitization is defined as rapid attenuation of receptor-mediated signaling. Recent studies report that multiple inhibitory GPCRs, including GABAB receptors, resist acute desensitization in the presynaptic but not postsynaptic compartments of certain neurons in mammal brains. In the present study, employing whole-cell voltage-clamp recordings on acute PAG slices from adult rats, we found that GABAB receptors resist acute desensitization to prolonged administration of baclofen (GABAB receptor agonist) in both presynaptic and postsynaptic compartments. The desensitization resistance of postsynaptic GABAB receptors was independent of presynaptic alteration and vice versa. The GABAB receptor-mediated inhibition at inhibitory presynaptic terminals also showed no desensitization. The results suggest that GABAB receptor-mediated inhibition remains functional in both postsynaptic and presynaptic compartments to sustained agonist administration in rat PAG neurons.

Bis[4-amino-3,5-bis-(pyridin-2-yl)-4H-1,2,4-triazole-κ(2)N(1),N(5)]diaqua-cobalt(II) bis-(perchlorate).

In the title structure, [Co(C(12)H(10)N(6))(2)(H(2)O)(2)](ClO(4))(2), the Co(II) atom lies on an inversion centre and is coordinated in a slightly distorted octa-hedral geometry by four N atoms from two 4-amino-3,5-bis-(pyridin-2-yl)-4H-1,2,4-triazole (adpt) ligands in equatorial positions and two O atoms from two water mol-ecules in axial positions. An intra-molecular N-H⋯N inter-action stabilizes the mol-ecular conformation. Inter-molecular N-H⋯O and O-H⋯O inter-actions involving the perchlorate counter-anions extend the monomeric compound into a two-dimensional network parallel to the bc plane.

Neural differentiation ability of mesenchymal stromal cells from bone marrow and adipose tissue: a comparative study.

BACKGROUND AIMS: The characteristics, such as morphologic and phenotypic characteristics and neural transdifferentiation ability, of mesenchymal stromal cells (MSC) derived from different origins have yet to be reported for cases isolated from the same individual. METHODS: The proliferation capacity, secretion ability of neurotrophins (NT) and neural differentiation ability in rat MSC isolated from bone marrow (BMSC) and adipose tissue (ADSC) were compared from the same animal. RESULTS: The ADSC had a significantly higher proliferation capacity than BMSC according to cell cycle and cumulative population doubling analyses. The proportion of cells expressing neural markers was greater in differentiated ADSC than in differentiated BMSC. Furthermore, the single neurosphere derived from ADSC showed stronger expansion and differentiation abilities than that derived from BMSC. The findings from Western blot lent further support to the immunocytochemical data. The mRNA and protein levels of nerve growth factor (NGF) and brain-derived growth factor (BDNF) expressed in ADSC were significantly higher than those in BMSC at different stages before and following induction. CONCLUSIONS: Our study suggests that the proliferation ability of ADSC is superior to that of BMSC. Furthermore, differentiated ADSC expressed higher percentages of neural markers. As one possible alternative source of BMSC, ADSC may have wide potential for treating central nervous system (CNS) diseases.

Bis(2-amino-5-methyl-1,3,4-thia-diazole-κN(3))dichloridocobalt(II).

In the monomeric title complex, [CoCl(2)(C(3)H(5)N(3)S)(2)], the Co(II) atom is tetra-coordinated by two chloride anions and two N atoms from two monodentate 2-amino-5-methyl-1,3,4-thia-diazole ligands, giving a slightly distorted tetra-hedral stereochemistry [bond angle range about Co = 105.16 (12)-112.50 (10)°]. In the complex, the dihedral angle between the 1,3,4-thia-diazole planes in the two ligands is 72.8 (1)°. There are two intra-molecular N-H⋯Cl inter-actions in the complex unit, while in the crystal, inter-molecular N-H⋯N and N-H⋯Cl hydrogen bonds link these units into a two-dimensional layered structure parallel to (011).

Bis[3-(pyrazin-2-yl)-5-(pyridin-2-yl-κN)-1,2,4-triazol-1-ido-κN(1)]copper(II).

In the mononuclear title complex, [Cu(C(11)H(7)N(6))(2)], the Cu(II) atom lies on a crystallographic inversion centre and is coordinated by four N atoms from two bidentate chelate monoanionic 3-(pyrazin-2-yl)-5-(pyridin-2-yl-1,2,4-triazol-1-ido ligands, two from the triazolide rings [Cu-N = 1.969 (2) Å] and two from the pyridine rings [Cu-N = 2.027 (2) Å], giving a slightly distorted square-planar geometry.

Potassium channels underlie postsynaptic but not presynaptic GABAB receptor-mediated inhibition on ventrolateral periaqueductal gray neurons.

γ-Aminobutyric acid (GABA) is the principle inhibitory neurotransmitter in adult mammalian brain. GABA receptors B subtype (GABA(B)Rs) are abundantly expressed at presynaptic and postsynaptic neuronal structures in the rat ventrolateral periaqueductal gray (PAG), an area related to pain regulation. Activation of GABA(B)Rs by baclofen, a selective agonist, induces presynaptic inhibition by decreasing presynaptic glutamate release. At the same time, baclofen induces a postsynaptic inhibitory membrane current or potential. We here report that in the ventrolateral PAG, the postsynaptic inhibition is mediated by activation of G protein-coupled inwardly rectifying K(+) (GIRK) channels. Blockade of K(+) channels largely prevents postsynaptic action of baclofen. In contrast, presynaptic inhibition of baclofen is insensitive to K(+) channel blockade. The data indicate that potassium channels play different roles in GABA(B)R-mediated presynaptic and postsynaptic inhibition on PAG neurons.

[Biocompatibility of a novel biological piezoelectric ceramic to the rat periosteum derived osteoblast].

OBJECTIVE: A novel biological piezoelectric ceramic was made by beta-tricalcium phosphate (beta-TCP) and lithium sodium potassium niobate (LNK) piezoelectric ceramics. To study its biocompatibility to osteoblast isolated from the cranium of 1-day-old Sprague-Dawley mice. METHODS: The biological piezoelectric ceramic TCPLNK1/10, TCPLNK5/5 respectively mixed by beta-TCP and LNK piezoelectric ceramic at the ratio of 1/10 and 5/5. Then osteoblasts were used and seeded respectively on the negative and positive surfaces of TCPLNK1/10 and TCPLNK5/5. Growth and proliferation of the osteoblasts on TCPLNK1/10 and TCPLNK5/5 surfaces were evaluated in vitro by means of scanning electron microscopy (SEM) examination, fluorescence dyeing of osteoblast skeleton protein and MTT assay. RESULTS: Cell morphology of osteoblast on positive and negative surfaces of TCPLNK1/10 and TCPLNK5/5 was normal, and both adhesion and growth characteristics showed better than control group. The growing osteoblasts on the TCPLNK1/10 negative surface were significantly higher than others. The negative surface of TCPLNK1/10 possessed better osteogenesis potential than others in vitro. CONCLUSION: The surface of TCPLNK may permit the imitation piezoelectric effect of natural bone for bone regeneration.

Tris(2,2'-bioxazoline-kappa2N,N')copper(II) diperchlorate and tris(2,2'-bioxazoline-kappa2N,N')nickel(II) diperchlorate.

In the two isomorphous title compounds, viz. tris[2,2'-bi(4,5-dihydro-1,3-oxazole)-kappa(2)N,N']copper(II) diperchlorate, [Cu(C6H8N2O2)3](ClO4)2, (I), and tris[2,2'-bi(4,5-dihydro-1,3-oxazole)-kappa2N,N']nickel(II) diperchlorate, [Ni(C6H8N2O2)3](ClO4)2, (II), the MII ions each have a distorted octahedral coordination geometry formed via six N atoms from three 2,2'-bioxazoline ligands. For each ligand, the two five-membered rings are nearly coplanar. It is noteworthy that the Jahn-Teller effect is stronger in (I) than in (II). The three-dimensional supramolecular structures of (I) and (II) are formed via weak hydrogen-bonding interactions between O atoms from perchlorate anions and H atoms from 2,2'-bioxazoline ligands.

[Responses of neurons and astrocytes in rat hippocampus to kainic acid-induced seizures].

OBJECTIVE: To investigate the time course of the responses of neurons and astrocytes in rat hippocampus (HI) to kainic acid (KA)-induced seizures in various regions. METHODS: By means immunohistochemical staining for anti-Fos protein and anti-glial fibrillary acidic protein (GFAP), the regional distribution of reactive neurons and astrocytes in the HI was observed at different time points after a unilateral stereotaxic microinjection of KA into the lateral ventricle of rats to cause limbic and generalized convulsive seizures. RESULTS: The injection of KA triggered limbic motor seizures including immobilization, staring, facial and jaw clonus ect. followed by recurrent generalized convulsive seizures. After KA-induced seizures, the GFAP-positive astrocytes and Fos-positive neurons were markedly increased in the HI. The increase of GFAP immunoreactivity was observed 30 min after the seizure onset, reaching the maximum at 1 h; the increase of Fos immunoreactivity was detected at 1 h after the onset, peaking at 2 h. CONCLUSION: The neurons and astrocytes in rat HI are highly active during seizures and the reactive astrocytes might play an important role in epileptogenesis.

Effect of kainate on the synaptic transmission in hippocampal CA1 region.

OBJECTIVE: To investigate the effect of activated kainate receptor on both the excitatory and inhibitory synaptic transmission in the neurons in the hippocampal CA1 region. METHOD: Blind whole-cell voltage-clamp recordings were performed on the CA1 pyramidal cells in adult rat hippocampal slices to examine and analyze the effect of bath-applied kainate (10 micromol/L) on CA1 afferent fiber-evoked excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs), respectively. RESULTS: Activation of kainate receptor significantly depressed both IPSCs (P <0.01) and EPSCs (P <0.01) in neurons in the hippocampus CA1 region. CONCLUSION: Activation of kainate receptors directly inhibit excitatory and inhibitory input in those neurons, which contributes to the development of epilepsy in the hippocampus by affecting the dynamic balance of the hippocampal neurons.