Discovery of orbital ordering in Bi2Sr2CaCu2O8+x.

The primordial ingredient of cuprate superconductivity is the CuO2 unit cell. Theories usually concentrate on the intra-atom Coulombic interactions dominating the 3d9 and 3d10 configurations of each copper ion. However, if Coulombic interactions also occur between electrons of the 2p6 orbitals of each planar oxygen atom, spontaneous orbital ordering may split their energy levels. This long-predicted intra-unit-cell symmetry breaking should generate an orbitally ordered phase, for which the charge transfer energy ε separating the 2p6 and 3d10 orbitals is distinct for the two oxygen atoms. Here we introduce sublattice-resolved ε(r) imaging to CuO2 studies and discover intra-unit-cell rotational symmetry breaking of ε(r). Spatially, this state is arranged in disordered Ising domains of orthogonally oriented orbital order bounded by dopant ions, and within whose domain walls low-energy electronic quadrupolar two-level systems occur. Overall, these data reveal a Q = 0 orbitally ordered state that splits the oxygen energy levels by ~50 meV, in underdoped CuO2.

Detection of a pair density wave state in UTe2.

Spin-triplet topological superconductors should exhibit many unprecedented electronic properties, including fractionalized electronic states relevant to quantum information processing. Although UTe2 may embody such bulk topological superconductivity1-11, its superconductive order parameter Δ(k) remains unknown12. Many diverse forms for Δ(k) are physically possible12 in such heavy fermion materials13. Moreover, intertwined14,15 density waves of spin (SDW), charge (CDW) and pair (PDW) may interpose, with the latter exhibiting spatially modulating14,15 superconductive order parameter Δ(r), electron-pair density16-19 and pairing energy gap17,20-23. Hence, the newly discovered CDW state24 in UTe2 motivates the prospect that a PDW state may exist in this material24,25. To search for it, we visualize the pairing energy gap with µeV-scale energy resolution using superconductive scanning tunnelling microscopy (STM) tips26-31. We detect three PDWs, each with peak-to-peak gap modulations of around 10 µeV and at incommensurate wavevectors Pi=1,2,3 that are indistinguishable from the wavevectors Qi=1,2,3 of the prevenient24 CDW. Concurrent visualization of the UTe2 superconductive PDWs and the non-superconductive CDWs shows that every Pi:Qi pair exhibits a relative spatial phase δϕ ≈ π. From these observations, and given UTe2 as a spin-triplet superconductor12, this PDW state should be a spin-triplet PDW24,25. Although such states do exist32 in superfluid 3He, for superconductors, they are unprecedented.

Investigation into Antiepileptic Effect of Ganoderic Acid A and Its Mechanism in Seizure Rats Induced by Pentylenetetrazole.

Ganoderic acid A (GAA) exhibited neuron protection in in vitro epilepsy study, but no study has been done in vivo. Rats were administered (i.p.) pentylenetetrazole daily for 28 days to induce seizure. Rats with grade II or above of epileptic score were divided into three groups and given placebo, sodium valproate, or GAA treatment, respectively, for 7 days. The electrical signals of brain were monitored with electroencephalography (EGG); epileptic behavior was assessed using the Racine scale; morphological changes and apoptosis rate of cortical neurons were assessed with H&E staining and TUNEL staining, respectively. Protein expression of calcium-sensing receptor, p-ERK, p-JNK, and p-p38 in hippocampal tissue and Bcl-2, cleaved caspase-3, and Bax in cortical tissues was observed by Western blot and immunohistochemistry assay, respectively. After GAA treatment, apparent seizure-like EEG with significant arrhythmic disorder and spike waves was reduced or disappeared, and wave amplitude of EEG was reduced significantly. GAA showed similar effect with sodium valproate treatments on epilepsy. There were an apparent improvement of the epileptic behavior and a significant increase in the epileptic latency and shortening of the epileptic duration in the treatment group compared to control. GAA treatment ameliorated the nuclear pyknosis of neurons which appeared seriously in the epilepsy group. GAA treatment significantly reduced the cortical neuron apoptosis of epilepsy and the expression of calcium-sensing receptor, p-P38, p-JNK, cleaved caspase-3, and Bax but increased the expression of both p-ERK and Bcl-2. In conclusion, GAA treatment showed strong antiepileptic effect by decreasing apoptosis in cortical neuron and the expression of calcium-sensing receptor and stimulating the MAPK pathway.

Metformin Can Enhance the Inhibitory Effect of Olaparib in Bladder Cancer Cells.

Background: Bladder cancer is a common urinary system tumor. In the treatment of clinical patients, it is particularly important to find an effective treatment method to inhibit tumor growth. The world's first PARP inhibitor olaparib is mainly used for the treatment of BRCA1/BRCA2 mutated tumors. Metformin, an antidiabetic drug, has been reported to reduce cancer incidence in humans and improve survival in cancer patients. Methods: Cell viability and proliferation were detected by CCK-8 assay and colony formation assay; cell apoptosis was detected by flow cytometry; cell migration and invasion abilities were detected by scratch assay and Transwell assay; STAT3/C-MYC signaling pathway protein were detected by western blotting. Results: Olaparib combined with metformin has better effects on the proliferation, clone formation, migration, invasion, and apoptosis of bladder cancer cells than single drug, indicating that metformin can enhance the inhibitory effect of olaparib on tumor growth and regulate the expression of STAT3/C-MYC signaling pathway proteins. Conclusion: The results of this study showed that metformin could significantly enhance the antitumor effect of olaparib on bladder cancer cells, and these effects were mediated by downregulating STAT3/C-MYC signaling pathway proteins. This finding may have potential clinical application in the treatment of bladder cancer.

LncRNA ZFAS1 regulates the hippocampal neurons injury in epilepsy through the miR-15a-5p/OXSR1/NF-κB pathway.

Long non-coding RNAs (lncRNAs) have been confirmed to be involved in epilepsy development. It has been reported that lncRNA ZFAS1 plays a vital regulatory role in epilepsy progression. Therefore, the role and molecular mechanism of ZFAS1 in epilepsy progression deserve further investigation. Mice status epilepticus (SE) model was constructed, and hippocampal neurons were isolated from mice hippocampus tissues. The expression of ZFAS1, miR-15a-5p and oxidative stress responsive 1 (OXSR1) were determined by quantitative real-time PCR. ELISA assay was used to detect the concentrations of inflammation factors. Cell viability and apoptosis were examined by MTT assay, EdU staining and flow cytometry. Western blot analysis was conducted to measure protein levels, and the productions of SOD and MDA were measured to assess cell oxidative stress. Dual-luciferase reporter assay and RIP assay were employed to validate the relationship between miR-15a-5p and ZFAS1 or OXSR1. LncRNA ZFAS1 was highly expressed in SE mice and SE-stimulated hippocampal neurons. Silenced ZFAS1 promoted viability, while inhibited inflammation, apoptosis and oxidative stress in SE-induced hippocampal neurons. MiR-15a-5p could be targeted by ZFAS1, and its inhibitor also reversed the suppressive effect of ZFAS1 knockdown on SE-induced hippocampal neurons injury. In addition, OXSR1 was a target of miR-15a-5p, and its silencing also could relieve SE-induced hippocampal neurons injury. OXSR1 overexpression reversed the inhibition effect of miR-15a-5p on SE-induced hippocampal neurons injury. Moreover, ZFAS1 positively regulated OXSR1 expression by sponging miR-15a-5p, thereby activating the NF-κB pathway. LncRNA ZFAS1 might contribute to the progression of epilepsy by regulating the miR-15a-5p/OXSR1/NF-κB pathway.

Effects and Mechanism of Ganoderma lucidum Polysaccharides in the Treatment of Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats.

Ganoderma lucidum polysaccharides (GLP) have renal protection effect but there was no study on the diabetic nephropathy. This study was designed to investigate its effect and mechanism using a diabetic rat model induced by streptozotocin (50 mg/kg, i.p.). The diabetic rats were treated with GLP (300 mg/kg/day) for 10 weeks. The blood glucose, glycated hemoglobin, body weight, and the levels of blood creatinine, urea nitrogen, and urine protein were assessed. And renal pathologies were assessed by the tissue sections stained with hematoxylin-eosin, Masson's trichome, and periodic acid-Schiff. The expression of phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR), the autophagy proteins beclin-1, LC3-II, LC3-I, and P62; the apoptosis-related proteins caspase-3 and caspase-9; and the inflammation markers IL-6, IL-1ß, and TNF-ɑ were assessed. Results showed that GLP alleviated the impairment of renal function by reducing urinary protein excretion and the blood creatinine level and ameliorated diabetic nephropathy. The expression of p-PI3K, p-Akt, and p-mTOR in the diabetic kidney were significantly reduced in the GLP treatment group compared to the without treatment group. GLP treatment activated the autophagy indicators of beclin-1 and the ratio of LC3-II/LC3-I but reduced p62 and also inhibited the expression of caspase-3, caspase-9 and IL-6, IL-1ß, and TNF-ɑ. In conclusion, the effect of GLP amelioration diabetic nephropathy may be via the PI3k/Akt/mTOR signaling pathway by inhibition of the apoptosis and inflammation and activation of the autophagy process.

Scattering interference signature of a pair density wave state in the cuprate pseudogap phase.

An unidentified quantum fluid designated the pseudogap (PG) phase is produced by electron-density depletion in the CuO2 antiferromagnetic insulator. Current theories suggest that the PG phase may be a pair density wave (PDW) state characterized by a spatially modulating density of electron pairs. Such a state should exhibit a periodically modulating energy gap [Formula: see text] in real-space, and a characteristic quasiparticle scattering interference (QPI) signature [Formula: see text] in wavevector space. By studying strongly underdoped Bi2Sr2CaDyCu2O8 at hole-density ~0.08 in the superconductive phase, we detect the 8a0-periodic [Formula: see text] modulations signifying a PDW coexisting with superconductivity. Then, by visualizing the temperature dependence of this electronic structure from the superconducting into the pseudogap phase, we find the evolution of the scattering interference signature [Formula: see text] that is predicted specifically for the temperature dependence of an 8a0-periodic PDW. These observations are consistent with theory for the transition from a PDW state coexisting with d-wave superconductivity to a pure PDW state in the Bi2Sr2CaDyCu2O8 pseudogap phase.

Central Blockade of E-Prostanoid 3 Receptor Ameliorated Hypertension Partially by Attenuating Oxidative Stress and Inflammation in the Hypothalamic Paraventricular Nucleus of Spontaneously Hypertensive Rats.

Hypertension, as one of the major risk factors for cardiovascular disease, significantly affects human health. Prostaglandin E2 (PGE2) and the E3-class prostanoid (EP3) receptor have previously been demonstrated to modulate blood pressure and hemodynamics in various animal models of hypertension. The PGE2-evoked pressor and biochemical responses can be blocked with the EP3 receptor antagonist, L-798106 (N-[(5-bromo-2methoxyphenyl)sulfonyl]-3-[2-(2-naphthalenylmethyl) phenyl]-2-propenamide). In the hypothalamic paraventricular nucleus (PVN), sympathetic excitation can be introduced by PGE2, which can activate EP3 receptors located in the PVN. In such a case, the central knockdown of EP3 receptor can be considered as a potential therapeutic modality for hypertension management. The present study examined the efficacy of the PVN infusion of L-798106, by performing experiments on spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). The rats were administered with chronic bilateral PVN infusion of L-798106 (10 µg/day) or the vehicle for 28 days. The results indicated that the SHRs had a higher mean arterial pressure (MAP), an increased Fra-like (Fra-LI) activity in the PVN, as well as a higher expression of gp91phox, mitogen-activated protein kinase (MAPK), and proinflammatory cytokines in the PVN compared with the WKYs. Additionally, the expression of Cu/Zn-SOD in the PVN of the SHRs was reduced compared with the WKYs. The bilateral PVN infusion of L-798106 significantly reduced MAP, as well as plasma norepinephrine (NE) levels in the SHRs. It also inhibited Fra-LI activity and reduced the expression of gp91phox, proinflammatory cytokines, and MAPK, whereas it increased the expression of Cu/Zn-SOD in the PVN of SHRs. In addition, L-798106 restored the balance of the neurotransmitters in the PVN. On the whole, the findings of the present study demonstrate that the PVN blockade of EP3 receptor can ameliorate hypertension and cardiac hypertrophy partially by attenuating ROS and proinflammatory cytokines, and modulating neurotransmitters in the PVN.

Effect and Mechanism of Ganoderma lucidum Spores on Alleviation of Diabetic Cardiomyopathy in a Pilot in vivo Study.

BACKGROUND: Ganoderma lucidum spores (GLS) exhibit disease prevention properties, but no study has been carried out on the anti-diabetic cardiomyopathy property of GLS. The aim of this study was to evaluate the hyperglycemia-mediated cardiomyopathy protection and mechanisms of GLS in streptozotocin (STZ)induced diabetic rats. METHODS: Male SD rats were randomly divided into three groups. Two groups were given STZ (50 mg/kg, i.p.) treatment and when their fasting plasma glucose was above 16.7 mmol/L, among them, one group was given placebo, as diabetic group, and another group was given GLS (300 mg/kg) treatment. The group without STZ treatment was given placebo as a control group. The experiment lasted 70 days. The histology of myocardium and biomarkers of antioxidants, myocardial injury, pro-inflammatory cytokines, pro-apoptotic proteins and phosphorylation of key proteins in PI3K/AKT pathway were assessed. RESULTS: Biochemical analysis showed that GLS treatment significantly reduced the blood glucose (-20.3%) and triglyceride (-20.4%) levels compared to diabetic group without treatment. GLS treatment decreased the content of MDA (-25.6%) and activity of lactate dehydrogenase (-18.9%) but increased the activity of GSH-Px (65.4%). Western blot analysis showed that GLS treatment reduced the expression of both alpha-smooth muscle actin and brain natriuretic peptide. Histological analysis on the cardiac tissue micrographs showed that GLS treatment reduced collagen fibrosis and glycogen reactivity in myocardium. Both Western blot and immunohistochemistry analyses showed that GLS treatment decreased the expression levels of pro-inflammatory factors (cytokines IL-1ß, and TNF-α) as well as apoptosis regulatory proteins (Bax, caspase-3 and -9), but increased Bcl-2. Moreover, GLS treatment significantly increased the phosphorylation of key proteins involved in PI3K/AKT pathway, eg, p-AKT p-PI3K and mTOR. CONCLUSION: The results indicated that GLS treatment alleviates diabetic cardiomyopathy by reducing hyperglycemia, oxidative stress, inflammation, apoptosis and further attenuating the fibrosis and myocardial dysfunction induced by STZ through stimulation of the PI3K/Akt/mTOR signaling pathway.

Associated Targets of the Antioxidant Cardioprotection of Ganoderma lucidum in Diabetic Cardiomyopathy by Using Open Targets Platform: A Systematic Review.

Even with substantial advances in cardiovascular therapy, the morbidity and mortality rates of diabetic cardiomyopathy (DCM) continually increase. Hence, a feasible therapeutic approach is urgently needed. Objectives. This work is aimed at systemically reviewing literature and addressing cell targets in DCM through the possible cardioprotection of G. lucidum through its antioxidant effects by using the Open Targets Platform (OTP) website. Methods. The OTP website version of 19.11 was accessed in December 2019 to identify the studies in DCM involving G. lucidum. Results. Among the 157 cell targets associated with DCM, the mammalian target of rapamycin (mTOR) was shared by all evidence, drug, and text mining data with 0.08 score association. mTOR also had the highest score association 0.1 with autophagy in DCM. Among the 1731 studies of indexed PubMed articles on G. lucidum published between 1985 and 2019, 33 addressed the antioxidant effects of G. lucidum and its molecular signal pathways involving oxidative stress and therefore were included in the current work. Conclusion. mTOR is one of the targets by DCM and can be inhibited by the antioxidative properties of G. lucidum directly via scavenging radicals and indirectly via modulating mTOR signal pathways such as Wnt signaling pathway, Erk1/2 signaling, and NF-κB pathways.

Mass balance and elimination mechanism of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) during the kraft pulping process.

Papermaking raw materials are usually digested by NaOH and Na2S solution. The fate of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) during the kraft pulping process is still poorly known. In this study, a comprehensive investigation was conducted on the variation in PCDD/Fs in the kraft pulping section of 3 modern non-wood pulp mills adopting elemental chlorine-free (ECF) bleaching technology. Similar dioxin homologue profiles, dominated by Cl1-3DF and Cl2DD homologues, were observed in the raw materials, black liquors and brown pulps; and the partitioning behaviors of dioxin congeners between black liquor and brown pulp were found to be partly dependent on their octanol-water partitioning coefficients. Dioxin mass flow analysis indicated that the raw materials contributed more than 95 % to the dioxins entering the pulping section. Approximately 7 - 30 % of the input dioxins were exported by black liquor, and the brown pulp carried 44 - 51 % of the input dioxins into the subsequent bleaching section. The kraft pulping process caused a 40 - 48 % reduction in input dioxins. Alkaline hydrolysis and coupling reaction between dioxins and the aromatic fragments of lignin were proposed as two most possible mechanisms for dioxin elimination. In general, modern pulp mills have actually become industrial plants that eliminate environmental dioxins.

Ferulic acid ameliorates pentylenetetrazol-induced seizures by reducing neuron cell death.

To investigate the neuroprotective effect of ferulic acid (FA) in a pentylenetetrazol (PTZ)-induced seizures model in rat, the motor response, spatial learning ability and memory capability of the rats were assessed. Both the antioxidation and anti-apoptosis pathways were also investigated. In this study, male Wistar rats were randomly divided into 3 groups (n = 12 in each group). For 28 days, the rats were administered saline alone (i.p. normal saline, NS group), PTZ (40 mg/kg, i.p., PTZ group) once daily to induce seizures, or FA (i.p. 60 mg/kg) 20 min before being given PTZ (40 mg/kg, i.p., FA + PTZ group) to assess the neuroprotective effect of FA. The motor response of the rats was analysed with the Racine scale. The spatial learning and memory capacity of the rats were assessed by the Morris water maze test. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured, and both in situ staining with the DNA-binding bisbenzimide Hoechst 33258 and TUNEL assays were used to assess apoptosis. Western blotting was used to further analyse the expression of Apaf-1, caspase-9, caspase-3, Bcl-2, Bid, Bax, cleaved caspase-3 and cytochrome c. The results showed that compared to the those of the PTZ group, FA pre-treatment significantly (p < 0.01) reduced the Racine scores starting at day 4, prolonged the latency of the onset of seizure at day 28, reduced the escape latency period starting at day 2, increased the frequency of crossing the platform location, increased the SOD activity, reduced the MDA content and apoptosis percentage, and upregulated the Bcl-2 levels whilst downregulating the Bax, cytochrome c, Apaf-1, caspase-9, caspase-3, cleaved caspase-3 and Bid expression levels. This study demonstrated that pre-treatment with FA exerts strong neuroprotective effects by reducing the motor response and by improving spatial learning ability and memory capacity. The neuroprotective effect may be a result of a reduction in neuron cell death that occurs via the antioxidative and anti-apoptotic pathways.

Influence of the support on stabilizing local defects in strained monolayer oxide films.

Two-dimensional materials with a honeycomb lattice, such as graphene and hexagonal boron nitride, often contain local defects in which the hexagonal elements are replaced by four-, five-, seven-, and eight-membered rings. An example is the Stone-Wales (S-W) defect, where a bond rotation causes four hexagons to be transformed into a cluster of two pentagons and two heptagons. A further series of similar defects incorporating divacancies results in larger structures of non-hexagonal elements. In this paper, we use scanning tunneling microscopy (STM) and density functional theory (DFT) modeling to investigate the structure and energetics of S-W and divacancy defects in a honeycomb (2 × 2) Ti2O3 monolayer grown on an Au(111) substrate. The epitaxial rumpled Ti2O3 monolayer is pseudomorphic and in a state of elastic compression. As a consequence, divacancy defects, which induce tension in freestanding films, relieve the compression in the epitaxial Ti2O3 monolayer and therefore have significantly lower energies when compared with their freestanding counterparts. We find that at the divacancy defect sites there is a local reduction of the charge transfer between the film and the substrate, the rumpling is reduced, and the film has an increased separation from the substrate. Our results demonstrate the capacity of the substrate to significantly influence the energetics, and hence favor vacancy-type defects, in compressively strained 2D materials. This approach could be applied more broadly, for example to tensile monolayers, where vacancy-type defects would be rare and interstitial-type defects might be favored.

CXCL5, the upregulated chemokine in patients with uterine cervix cancer, in vivo and in vitro contributes to oncogenic potential of Hela uterine cervix cancer cells.

CXCL5 is showed a surprisingly elevated profile and implicated in tumorigenesis in several tumors. However, the expression and function of CXCL5 in uterine cervix cancer (UCC) remain largely unknown. The current study aimed to elucidate the expression pattern of CXCL5 in human UCC tissues and Hela cervix cancer cell, as well as its functions in Hela cells. Our data showed that CXCL5 and its receptor CXCR2 were expressed by Hela uterine cervix cancer cells. CXCL5 was upregulated in UCC tissues, and its overexpression was positively correlated with age, but did not correlate with clinical stages and tumor infiltration. Exogenous administration of CXCL5 and CXCL5 overexpression contributed to proliferation and migration activities of Hela cells in vitro, consistent with this, CXCL5 overexpression also promoted growth of Hela cells in a nude mouse xenograft model. At the gene level, CXCL5 overexpression regulated the expression of tumor-related genes including ERK, p-ERK, AKT, p-AKT, DIABOL, NUMB, NDRG3 and CXCR2. Taken together, CXCL5 may contribute to a dominant role in UCC progression and sever as a potential molecular therapeutic target for UCC.

Bioaccumulation and human health risks of OCPs and PCBs in freshwater products of Northeast China.

The levels and spatial distribution of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in freshwater products from Northeast China were investigated by gas chromatography coupled to isotope dilution high-resolution mass spectrometry. All samples were on-spot sampled from main production regions of freshwater products in Northeast China, and these samples were used to systematically assess the potential health risks of OCPs and PCBs associated with consumption of these fishery products. Dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexane (HCHs), hexachlorobenzene (HCB) and PCBs were the major pollutants with 100% detection rates, and their levels ranged from 0.086 to 58, 0.038-3.3, 0.093-4.5 and 0.032-1.4 ng g-1 wet weight, respectively. The estimated dietary intakes of these contaminants were all below their corresponding acceptable daily intakes. Significant regional differences in the levels of OCPs and PCBs (P ≦ 0.001) were found in samples from Liaoning and Inner Mongolia. The results showed that the concentrations of targeted contaminants in aquatic products had species-specific characteristics, and the levels of targeted pollutants in Oncorhynchus mykiss and Eriocheir sienesis were significantly higher than those in other aquatic product species. Advisories on ten species of aquatic products suggested that consumption of Eriocheir sinensis, Oncorhynchus mykiss and Cyprinus carpio at a rate exceeding 15 meals per month would pose a cancer risk. A health risk assessment indicated that exposure to these pollutants through freshwater products consumption would cause a non-ignorable potential carcinogenic risk to humans.

Maximising the resolving power of the scanning tunneling microscope.

The usual way to present images from a scanning tunneling microscope (STM) is to take multiple images of the same area, to then manually select the one that appears to be of the highest quality, and then to discard the other almost identical images. This is in contrast to most other disciplines where the signal to noise ratio (SNR) of a data set is improved by taking repeated measurements and averaging them. Data averaging can be routinely performed for 1D spectra, where their alignment is straightforward. However, for serial-acquired 2D STM images the nature and variety of image distortions can severely complicate accurate registration. Here, we demonstrate how a significant improvement in the resolving power of the STM can be achieved through automated distortion correction and multi-frame averaging (MFA) and we demonstrate the broad utility of this approach with three examples. First, we show a sixfold enhancement of the SNR of the Si(111)-(7 × 7) reconstruction. Next, we demonstrate that images with sub-picometre height precision can be routinely obtained and show this for a monolayer of Ti2O3 on Au(111). Last, we demonstrate the automated classification of the two chiral variants of the surface unit cells of the (4 × 4) reconstructed SrTiO3(111) surface. Our new approach to STM imaging will allow a wealth of structural and electronic information from surfaces to be extracted that was previously buried in noise.

High C-X-C motif chemokine 5 expression is associated with malignant phenotypes of prostate cancer cells via autocrine and paracrine pathways.

The present study aimed to examine the effects and mechanisms of exogenous C-X-C motif chemokine 5 (CXCL5) and lentiviral CXCL5 overexpression on the regulation of malignant behaviors of prostate cancer cells in vitro and in a nude mouse xenograft model. The expression levels of CXCL5 and a number of tumor-related genes were assessed by using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, ELISA, or immunohistochemistry in normal and cancerous prostate cells and tissues. Cell proliferation, colony formation, and Transwell assays were performed to determine the effects of exogenous, autocrine, and paracrine CXCL5 on prostate cancer cell proliferative and migratory capacity. The results indicated that CXCL5 expression was upregulated in PC­3 and DU145 prostate cancer cells, in WPMY­1 normal prostate stromal cells, and in RWPE­1 prostate epithelial cells, as well as in prostate cancer tissue specimens. Exogenous CXCL5 exposure resulted in increase in prostate cancer cell proliferation, colony formation, and migration. In cells transfected with a CXCL5 overexpression vector, in cells cultured in conditioned medium from CXCL5-overexpressing WPMY cells, and in cells co-cultured with CXCL5­OE WPMY cells prostate cancer cell malignant phenotypes were induced in an autocrine/paracrine fashion in vitro; similar results were observed in nude mouse xenografts. CXCL5 overexpression also regulated expression of tumor-related genes, including BAX, N-Myc downstream-regulated gene 3, extracellular signal-regulated kinase 1/2, C-X-C chemokine receptor type 2, interleukin 18, Bcl­2, and caspase­3. These data demonstrated that CXCL5 expression was upregulated in prostate cancer tissues and that exogenous CXCL5 protein exposure or CXCL5 overexpression promoted malignant phenotypes of prostate cancer cells in vitro and in vivo.

Effects of ganoderic acid A on lipopolysaccharide-induced proinflammatory cytokine release from primary mouse microglia cultures.

For several thousand years, Ganoderma lucidum (Ling-Zhi in Chinese and Reishi in Japanese) has been widely used as a traditional medication for the prevention and treatment of various diseases in Asia. Its major biologically active components, ganoderic acids (GAs), exhibit significant medicinal value due to their anti-inflammatory effects. Dysregulation of microglial function may cause seizures or promote epileptogenesis through release of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α. At present, only little information is available on the effects of GAs on microglia-mediated inflammation in vitro and/or in vivo. The present study aimed to investigate the role of GA-A on microglia-mediated inflammation in vitro. In addition, the effect of GA-A on lipopolysaccharide (LPS)-evoked alterations in mitochondrial metabolic activity of microglia was evaluated. The results of the present study demonstrated that GA-A significantly decreased LPS-induced IL-1ß, IL-6 and TNF-α release from mouse-derived primary cortical microglial cells in a concentration-dependent manner. GA-A treatment reduced LPS-induced expression of nuclear factor (NF)-κB (p65) and its inhibitor, demonstrating that non-toxic suppression of IL-1ß, IL-6 and TNF-α production by GA-A is, at least in part, due to suppression of the NF-κB signaling pathway. In addition, the LPS-induced stimulation of mitochondrial activity of microglial cells was abolished by co-treatment with GA-A. Thus, GA-A treatment may be a potential therapeutic strategy for epilepsy prevention by suppressing microglia-derived proinflammatory mediators.

CXCL5 as an autocrine or paracrine cytokine is associated with proliferation and migration of hepatoblastoma HepG2 cells.

C-X-C motif chemokine ligand 5 (CXCL5) is a CXC-type chemokine that is a crucial inflammatory mediator and a powerful attractant for granulocytic immune cells. Increasing evidence has indicated that CXCL5 is involved in the tumorigenesis of various malignancies. The present investigation demonstrated that CXCL5 was expressed in both hepatoblastoma HepG2 cells and liver stellate LX-2 cells, and CXCL5's receptor C-X-C chemokine receptor type 2 (CXCR2) was expressed in HepG2 cells by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and ELISA assays. Cell counting kit-8, colony formation and Transwell assays revealed that exogenous CXCL5 expression efficiently promoted proliferation, colony formation and migration of HepG2 cells. To explore the autocrine and paracrine roles of CXCL5 in the oncogenic potential of HepG2 cells, HepG2 cells overexpressing CXCL5 and LX-2 cells overexpressing CXCL5 were successfully constructed by gene transfection. Similarly, overexpression of CXCL5 in HepG2 also enhanced proliferation, colony formation and migration of HepG2 cells. Furthermore, the condition medium of LX-2 cells overexpressing CXCL5 affected the proliferation and migration of HepG2 cells. RT-PCR and western blotting assays were also conducted to explore whether overexpression of CXCL5 in HepG2 modulated the expression of genes. The results revealed that overexpression of CXCL5 regulated the expression of several genes, including N-myc downregulated gene 3,w B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, P53, vascular endothelial growth factor, interleukin (IL)-18, IL-1ß and cystathionine-γ-lyase. In conclusion, the present findings indicate that CXCL5/CXCR2 axis contributes to the oncogenic potential of hepatoblastoma via autocrine or paracrine pathways by regulating expression of genes associated with the progression of carcinoma.