Acmella oleracea (L.) is a plant popularly known as jambu in the Brazilian Amazon. This species has several biological properties, such as anaesthetic, antioxidant and anti-inflammatory activities, ...among others. However, there is limited information on its anticancer activity. In this context, this study aims to evaluate the effects of the hydroethanolic extract of jambu and its active compound (spilanthol) on gastric cancer cells. Hydroethanolic jambu inflorescence extract was obtained, and spilanthol was isolated by HPLC. Biological cytotoxicity assays were determined using MTT tests. In addition, an in silico study using molecular docking evaluated the inhibitory properties of spilanthol against JAK1 and JAK2 proteins. The results showed that the hydroethanolic extract and the isolated compound spilanthol exhibited cytotoxicity against cancer cells. Molecular docking revealed that spilanthol has inhibitory potential for JAK1 and JAK2 proteins. Thus, extract of jambu and spilanthol can be a possible candidate for the treatment of gastric carcinoma.
We have developed a method for determining interplanetary coronal mass ejection (ICME) geometry from galactic cosmic ray data recorded by the ground‐based muon detector network. The cosmic ray ...density depression inside the ICME, which is associated with a Forbush decrease, is represented by an expanding cylinder that is based on a theoretical model of the cosmic ray particle diffusion. ICME geometry and orientation are deduced from observed time variations of cosmic ray density and density gradient and are compared with those deduced from a magnetic flux rope model. From March 2001 to May 2005, 11 ICME events that produced Forbush decreases >2% were observed, and clear variations of the density gradient due to ICME passage were observed in 8 of 11 events. In five of the eight events, signatures of magnetic flux rope structure (large, smooth rotation of magnetic field) were also seen, and the ICME geometry and orientation deduced from the two methods were very similar in three events. This suggests that the cosmic ray‐based method can be used as a complementary method for deducing ICME geometry especially for events where a large Forbush decrease is observed.
We analyze the temporal variation of the diurnal anisotropy of sub-TeV cosmic-ray intensity observed with the Matsushiro (Japan) underground muon detector over two full solar activity cycles in ...1985-2008. We find an anisotropy component in the solar diurnal anisotropy superimposed on the Compton-Getting anisotropy due to Earth's orbital motion around the Sun. The phase of this additional anisotropy is almost constant at {approx}15:00 local solar time corresponding to the direction perpendicular to the average interplanetary magnetic field at Earth's orbit, while the amplitude varies between a maximum (0.043% +- 0.002%) and minimum ({approx}0.008% +- 0.002%) in a clear correlation with the solar activity. We find a significant time lag between the temporal variations of the amplitude and the sunspot number (SSN) and obtain the best correlation coefficient of +0.74 with the SSN delayed for 26 months. We suggest that this anisotropy might be interpreted in terms of the energy change due to the solar-wind-induced electric field expected for galactic cosmic rays (GCRs) crossing the wavy neutral sheet. The average amplitude of the sidereal diurnal variation over the entire period is 0.034% +- 0.003%, which is roughly one-third of the amplitude reported from air shower and deep-underground muon experiments monitoring multi-TeV GCR intensity suggesting a significant attenuation of the anisotropy due to the solar modulation. We find, on the other hand, only a weak positive correlation between the sidereal diurnal anisotropy and the solar activity cycle in which the amplitude in the 'active' solar activity epoch is about twice the amplitude in the 'quiet' solar activity epoch. This implies that only one-fourth of the total attenuation varies in correlation with the solar activity cycle and/or the solar magnetic cycle. We finally examine the temporal variation of the 'single-band valley depth' (SBVD) quoted by the Milagro experiment and, in contrast with recent Milagro's report, we find no steady increase in the Matsushiro observations in a seven-year period between 2000 and 2007. We suggest, therefore, that the steady increase of the SBVD reported by the Milagro experiment is not caused by the decreasing solar modulation in the declining phase of the 23rd solar activity cycle.
Background DAV‐interferon (IFN)‐β therapy is a combination chemotherapy of dacarbazine (DTIC), nimustine (ACNU) and vincristine (VCR) with local subcutaneous injection of IFN‐β that is widely ...employed as postoperative adjuvant chemotherapy to treat malignant melanoma in Japan. However, the efficacy of DAV‐IFN‐β therapy has not been confirmed by randomized controlled trials and the benefit of DAV‐IFN‐β therapy has not been established yet. This study evaluated the contribution of DAV‐IFN‐β therapy to improve survival of postoperative patients with cutaneous melanoma.
Methods Patients with stage II or III cutaneous melanoma seen at Nagoya University Hospital from January 1998 to December 2009 were eligible for this study. Disease‐free survival rates and melanoma‐specific survival rates were evaluated. A propensity score was calculated to control for the effects of variables related to decisions regarding the application of DAV‐IFN‐β therapy.
Results Eighty‐two stage II and 60 stage III melanoma patients were included. In the post‐matched stage II patients (17 matched pairs), the mean (±SE) disease‐free survival rates were 39.9±13.7% for DAV‐IFN‐β therapy and 73.1±11.7% for non‐use (hazard ratio for recurrence, 2.06; 95% CI, 0.63–6.69; P = 0.23), and the melanoma‐specific survival rates were 66.2±20.0% for DAV‐IFN‐β therapy and 86.2±9.1% for non‐use (hazard ratio for death, 1.09; 95% CI, 0.17–6.82; P = 0.93). In the post‐matched stage III patients (nine matched pairs), the disease‐free survival rates were 29.6±16.4% for DAV‐IFN‐β therapy and 33.3±15.7% for non‐use (0.69; 95% CI, 0.22–2.17; P = 0.53), and the melanoma‐specific survival rates were 55.6±16.6% for DAV‐IFN‐β therapy and 44.4±16.6% for non‐use (0.67; 95% CI, 0.18–2.50; P = 0.55).
Conclusions DAV‐IFN‐β therapy brought no significant improvement in either disease‐free survival rates or melanoma‐specific survival rates of patients with stage II or III cutaneous melanoma. A randomized controlled trial would be required to further evaluate the efficacy of DAV‐IFN‐β therapy as an adjuvant chemotherapy.
The wavelet transform technique has been applied to investigate the periodicities longer than a year in cosmic ray intensity variations observed at the Voyager spacecraft and at the Earth. We found ...significant ∼1.7‐ and ∼1.3‐year periodic components in the cosmic ray intensity variation in the outer heliosphere during the 1980s (solar cycle 21) and the 1990s (solar cycle 22), respectively. This property is consistent with the result of the wavelet analysis of the cosmic ray intensity variations observed at several Neutron Monitors (NMs) and also with previous reports about these periodicities using several plasma parameters, such as the solar wind speed and geomagnetic indices, for example. As comparing with the interplanetary magnetic field (IMF) and solar flare indices, causal relation between energy release from the Sun and the ∼1.7‐year quasi‐periodicity is suggested.
We present for the first time hourly variations of the spatial density gradient of 50 GeV cosmic rays within a sample solar rotation period in 2006. By inversely solving the diffusive flux equation, ...including the drift, we deduce the gradient from the anisotropy that is derived from the observation made by the Global Muon Detector Network (GMDN). The anisotropy obtained by applying a new analysis method to the GMDN data is precise and free from atmospheric temperature effects on the muon count rate recorded by ground- based detectors. We find the derived north-south gradient perpendicular to the ecliptic plane is oriented toward the heliospheric current sheet (HCS; i.e., southward in the toward sector of the interplanetary magnetic field IMF and northward in the away sector). The orientation of the gradient component parallel to the ecliptic plane remains similar in both sectors, with an enhancement of its magnitude seen after the Earth crosses the HCS. These temporal features are interpreted in terms of a local maximum of the cosmic ray density at the HCS. This is consistent with the prediction of the drift model for the image epoch. By comparing the observed gradient with the numerical prediction of a simple drift model, we conclude that particle drifts in the large-scale magnetic field play an important role in organizing the density gradient, at least in the present image epoch. We also found that corotating interaction regions did not have such a notable effect. Observations with the GMDN provide us with a new tool for investigating cosmic-ray transport in the IMF.
We analyze the precursor of a Forbush decrease (FD) observed with the Global Muon Detector Network on 2006 December 14. An intense geomagnetic storm is also recorded during this FD with the peak Kp ...index of 8+. By using the 'two-dimensional map' of the cosmic ray intensity produced after removing the contribution from the diurnal anisotropy, we succeed in extracting clear signatures of the precursor. A striking feature of this event is that a weak loss-cone (LC) signature is first recorded more than a day prior to the storm sudden commencement (SSC) onset. This suggests that the LC precursor appeared only 7 hr after the coronal mass ejection eruption from the Sun, when the interplanetary (IP) shock driven by the interplanetary coronal mass ejection was located at 0.4 AU from the Sun. We find the precursor being successively observed with multiple detectors in the network according to the Earth's spin and confirmed that the precursor continuously exists in space. The long lead time (15.6 hr) of this precursor which is almost twice the typical value indicates that the interplanetary magnetic field (IMF) was more quiet in this event than a typical power spectrum assumed for the IMF turbulence. The amplitude (-6.45%) of the LC anisotropy at the SSC onset is more than twice the FD size, indicating that the maximum intensity depression behind the IP shock is much larger than the FD size recorded at the Earth in this event. We also find the excess intensity from the sunward IMF direction clearly observed during {approx}10 hr preceding the SSC onset. It is shown that this excess intensity is consistent with the measurement of the particles accelerated by the head-on collisions with the approaching shock. This is the first detailed observation of the precursor due to the shock reflected particles with muon detectors.
Summary
Background Bowen's disease in the genital area is generally considered to be caused by mucosal high‐risk human papillomaviruses (HPVs). However, the detection rate and spectrum of HPVs in ...extragenital Bowen's disease are various and it is not clear to what extent HPV is involved in its pathogenesis.
Objectives To assess the degree of association of HPV in extragenital cases by examining detection rates, types, quantities and localization of HPV.
Methods A polymerase chain reaction (PCR) approach that we had previously established, which can give sensitive detection of a broad range of HPVs from cutaneous including epidermodysplasia verruciformis‐related HPVs (EV‐HPVs) to mucosal HPVs, was applied to samples from 41 patients with extragenital Bowen's disease and normal skin samples from 48 individuals. Semiquantitative L1‐PCR and tyramide‐based in situ hybridization (ISH) were also employed for positive cases.
Results HPVs belonging to the mucosal high‐risk group were detected in three patients with Bowen's disease (7%; two HPV 16 and one HPV 33), with 101−103 copy equivalents per diploid amount of cellular DNA. They were distributed among most nuclei of tumour cells but in none of the cells of adjacent normal skin. HPVs belonging to the cutaneous group were detected in two patients (5%; HPV 27 and HPV 76) at 10−2−10−3 copy equivalents, the same level as in a normal skin specimen positive for type 23 EV‐HPV. No positive signals were observed by ISH.
Conclusions HPVs belonging to the mucosal high‐risk group may participate in the development of extragenital Bowen's disease.
A coronal mass ejection (CME) associated with an X17 solar flare reached Earth on October 29, 2003, causing an ∼11% decrease in the intensity of high‐energy Galactic cosmic rays recorded by muon ...detectors. The CME also produced a strong enhancement of the cosmic ray directional anisotropy. Based upon a simple inclined cylinder model, we use the anisotropy data to derive for the first time the three‐dimensional geometry of the cosmic ray depleted region formed behind the shock in this event. We also compare the geometry derived from cosmic rays with that derived from in situ interplanetary magnetic field (IMF) observations using a Magnetic Flux Rope model.
Increased activity of intracellular glucocorticoid reactivating enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in obese adipose tissue contributes to adipose dysfunction. As recent ...studies have highlighted a potential role of preadipocytes in adipose dysfunction, we tested the hypothesis that a variety of metabolic stress mediated by ceramide or AMP-activated protein kinase (AMPK) would regulate 11β-HSD1 in preadipocytes. The present study is the first to show that 1) expression of 11β-HSD1 in 3T3-L1 preadipocytes was robustly induced when cells were treated with cell-permeable ceramide analogue C2 ceramide, bacterial sphingomyelinase, and sphingosine 1-phosphate, 2) 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR)-induced activation of AMPK augmented the expression and enzyme activity of 11β-HSD1, and 3) these results were reproduced in human preadipocytes. We demonstrate for the first time that C2 ceramide and AICAR markedly induced the expression of CCAAT/enhancer-binding protein (C/EBP) β and its binding to 11β-HSD1 promoter. Transient knockdown of C/EBPβ protein by small interfering RNA markedly attenuated the expression of 11β-HSD1 induced by C2 ceramide or AICAR. The present study provides novel evidence that ceramide- and AMPK-mediated signaling pathways augment the expression and activity of 11β-HSD1 in preadipocytes by way of C/EBPβ, thereby highlighting a novel, metabolic stress-related regulation of 11β-HSD1 in a cell-specific manner.
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