Neurotropin suppresses inflammatory cytokine expression and cell death through suppression of NF-κB and JNK in hepatocytes.

Inflammatory response and cell death in hepatocytes are hallmarks of chronic liver disease, and, therefore, can be effective therapeutic targets. Neurotropin® (NTP) is a drug widely used in Japan and China to treat chronic pain. Although NTP has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the action mechanism of NTP remains elusive. We hypothesize that NTP functions to suppress inflammatory pathways, thereby attenuating disease progression. In the present study, we investigated whether NTP suppresses inflammatory signaling and cell death pathways induced by interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) in hepatocytes. NTP suppressed nuclear factor-κB (NF-κB) activation induced by IL-1β and TNFα assessed by using hepatocytes isolated from NF-κB-green fluorescent protein (GFP) reporter mice and an NF-κB-luciferase reporter system. The expression of NF-κB target genes, Il6, Nos2, Cxcl1, ccl5 and Cxcl2 induced by IL-1β and TNFα was suppressed after NTP treatment. We also found that NTP suppressed the JNK phosphorylation induced by IL-1β and TNFα. Because JNK activation contributes to hepatocyte death, we determined that NTP treatment suppressed hepatocyte death induced by IL-1β and TNFα in combination with actinomycin D. Taken together, our data demonstrate that NTP attenuates IL-1β and TNFα-mediated inflammatory cytokine expression and cell death in hepatocytes through the suppression of NF-κB and JNK. The results from the present study suggest that NTP may become a preventive or therapeutic strategy for alcoholic and non-alcoholic fatty liver disease in which NF-κB and JNK are thought to take part

The Impact of Online Word-of-mouth and Negative Media Exposure on Consumer Habitual Skepticism: The Mediating Effect of Attribution

How did habitual skepticism come into being? In this research，the causes of consumer habitual skepticism are explored from the perspective of attribution. We put forward two important antecedent variables, negative online word-of-mouth and negative media exposure. The study results show that the higher the negative word-of-mouth perception is, the higher the stability and controllability of consumer attribution will be, and the higher the degree of consumer habitual skepticism will be. The higher the intensity of negative media exposure is, the higher the stability and controllability of consumer attribution will be, and the higher the degree of consumer habitual skepticism will be. We test this framework through two experiments. Study 1 investigates the influence of negative word-of-mouth spread and media exposure on consumer habitual skepticism. Study 2 investigates the effect of two independent variables on consumer habitual skepticism from an overall point of view and explore the mediation effect of attribution

Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers: implications for personalized cancer therapy

Information of antibodies used in immunohistochemistry. Table S2A. Relationship with clinicopathological factors-HGSC. Table S2B. Relationship with clinicopathological factors-CCC. Table S3 Association molecular biomarkers expression and platinum-based chemotherapeutic response. Table S4. Comparison of molecular biomarkers between recurrent and disease-free patients. (DOCX 42 kb

Surface analytical investigation on organometal triiodide perovskite

In a little over a year, there has been an unexpected breakthrough and rapid evolution of highly efficient solid-state hybrid solar cells based on organometal trihalide perovskite materials. This technology has the potential to produce solar cells with the very highest efficiencies while retaining the very lowest cost. The authors have measured the electronic density of states of CH3NH3PbI3 using ultraviolet photoemission spectroscopy (UPS), inverse photoemission spectroscopy (IPES), and x-ray photoemission spectroscopy (XPS). The valence band maximum and conduction band minimum positions are obtained from the UPS and IPES spectra, respectively, by linear extrapolation of the leading edges. The authors investigate the Au/perovskite and C60/perovskite interfaces by UPS and XPS. An interface dipole of 0.1 eV is observed at Au/perovskite interface. The energy levels of perovskite shift upward by ca.0.4 eV with Au coverage of 64Å upon it, resulting in band bending, hence a built-in field in perovskite that encourages hole transport to the interface. The XPS results show a strong initial shift of core levels to lower binding energy in the perovskite, which indicates that electrons transfer from the perovskite film to fullerene molecules. Further deposition of fullerene forms C60 solid, accompanied by the reduction of the electron transfer. The strongest electron transfer happened at 1/4 monolayer of fullerene

A Pilot Trial Assessing Urinary Gene Expression Profiling with an mRNA Array for Diabetic Nephropathy

BACKGROUND: The initiation and progression of diabetic nephropathy (DN) is complex. Quantification of mRNA expression in urinary sediment has emerged as a novel strategy for studying renal diseases. Considering the numerous molecules involved in DN development, a high-throughput platform with parallel detection of multiple mRNAs is needed. In this study, we constructed a self-assembling mRNA array to analyze urinary mRNAs in DN patients with aims to reveal its potential in searching novel biomarkers. METHODS: mRNA array containing 88 genes were fabricated and its performance was evaluated. A pilot study with 9 subjects including 6 DN patients and 3 normal controls were studied with the array. DN patients were assigned into two groups according to their estimate glomerular rate (eGFR): DNI group (eGFR>60 ml/min/1.73 m(2), n = 3) and DNII group (eGFR<60 ml/min/1.73 m(2), n = 3). Urinary cell pellet was collected from each study participant. Relative abundance of these target mRNAs from urinary pellet was quantified with the array. RESULTS: The array we fabricated displayed high sensitivity and specificity. Moreover, the Cts of Positive PCR Controls in our experiments were 24±0.5 which indicated high repeatability of the array. A total of 29 mRNAs were significantly increased in DN patients compared with controls (p<0.05). Among these genes, α-actinin4, CDH2, ACE, FAT1, synaptopodin, COL4α, twist, NOTCH3 mRNA expression were 15-fold higher than those in normal controls. In contrast, urinary TIMP-1 mRNA was significantly decreased in DN patients (p<0.05). It was shown that CTGF, MCP-1, PAI-1, ACE, CDH1, CDH2 mRNA varied significantly among the 3 study groups, and their mRNA levels increased with DN progression (p<0.05). CONCLUSION: Our pilot study demonstrated that mRNA array might serve as a high-throughput and sensitive tool for detecting mRNA expression in urinary sediment. Thus, this primary study indicated that mRNA array probably could be a useful tool for searching new biomarkers for DN