Potential redox-sensitive Akt activation by dopamine activates Bad and promotes cell death in melanocytes

Dopamine (DA) is a well known oxidative neurotoxin. In addition, Akt has been reported to deliver a survival signal that inhibits apoptosis. However, it has also been reported that chronic Akt activation leads to apoptosis in response to oxidative stress. The objective of the present study was to investigate the possible role of the Akt pathway in vitiligo and its possible relationship with DA-induced cell death using Mel-Ab cells. Cultured Mel-Ab cells were treated with DA with and without N-Acetyl-L-cysteine (NAC), which is known to have antioxidative properties. Cell viability was then assessed by a crystal violet assay and Annexin staining was performed. The changes in the expression of Akt were analyzed by western blot analysis. The cell viability was reduced by approximately 60% in response to treatment with 500 µM DA, and NAC effectively prevented this cytotoxic effect. Likewise, treatment with DA produced numerous Annexin positive cells, while treatment with NAC prevented this apoptotic cell death. Akt was slowly phosphorylated after treatment with DA, while NAC clearly inhibited the DA-induced Akt activation. Western blot analysis also showed that treatment with DA induced the activation of Bad. Finally, LY294002 exerted a protective effect against DA-induced apoptotic cell death. DA may induce redox-sensitive Akt activation and increase the level of Bad, which can promote cell death by heterodimerization with survival proteins. Moreover, NAC effectively protects against DA-induced melanocyte death via inhibition of DA-induced Akt activation

Schwannoma of ascending colon treated by laparoscopic right hemicolectomy

Schwannomas of the colon are rare and are difficult to diagnose preoperatively, since they often defy endoscopic and radiographic detection. Immunohistochemical stains are useful postoperatively to confirm this tumor, but more reliable diagnostic techniques (such as colonoscopic biopsy with immunohistochemistry) have emerged to enhance preoperative diagnostic accuracy. Here we report an instance of schwannoma arising in the ascending colon, where immunohistochemical staining of a preoperative biopsy facilitated diagnosis. After laparoscopic resection, histologic examination was confirmatory

Effects of Murine Dermal Cells on the Regulation of Hair Growth Is Dependent on the Cell Number and Post-Natal Age of Newborn Mice

Dermal cells from neonatal mice can initiate the formation of hair follicles (HFs) when combined with adult mouse epidermal cells and transplanted subcutaneously into athymic mice. In the present study, the effects of dermal cells on HF formation were tested in terms of total cell number and the time course of cell harvest. Results demonstrated that the number of dermal cells is critical to the formation of HF. Furthermore, hair forming ability is rapidly decreasing as the neonatal mice age. To examine potential differences in gene expression, cDNA array was performed. Results demonstrate that numerous molecules which are directly involved in receptor and signaling correlated with decreased hair inductivity in early time points after delivery. It is reported that bone morphogenic protein (BMP)-6 and Wnt3a treatment increased hair inductivity of dermal papilla cells. But in our study, no changes were observed in the expression levels of BMP-6 and Wnt3a. However, several Wnt related genes demonstrate increased or decreased expression levels. Thus, our results suggest that co-ordinated regulation of these molecules will be important in hair neogenesis within our model system

The Use of Complementary and Alternative Medicine in a General Population in South Korea: Results from a National Survey in 2006

The purpose of this survey was to obtain information on the prevalence, costs, and patterns of use of complementary and alternative medicine (CAM) in a general population in the Republic of Korea. In 2006, we conducted nationwide and population-weighted personal interviews with 6,021 adults ranging from 30 to 69 yr of age; the final sample consisted of 3,000 people with a 49.8% response rate. In addition to their general socio-demographics, the respondents were asked about their use of CAM during the previous 12-month period, costs, sources of information, and reasons for use. The prevalence of use overall was 74.8%, while biologically based CAM therapies were the most likely type of use (65.4%). The median annual out-of-pocket expenditures for CAM therapies was about US$203. The primary reason for using CAM was for disease prevention and health promotion (78.8%). The main source of advice about CAM therapies use was most likely to be from family and friends (66.9%). Our study suggests that CAM use has been and continues to be very popular in South Korea. Conventional western medical doctors and governments should obtain more evidence and become more interested in CAM therapies

A phase 2a double-blind, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of NuGel, a novel topical GPCR19-mediated inflammasome inhibitor, in patients with mild to moderate atopic dermatitis: a proof-of-concept study with Post-hoc biomarker analysis

BackgroundCurrent guidelines to treat atopic dermatitis (AD) overlook disease heterogeneity, limiting personalized care. This study assessed NuGel, a topical GPCR19 agonist, for efficacy, safety, and predictive baseline biomarkers in AD patients.MethodsIn a multicenter, double-blind, randomized, placebo-controlled Phase 2a trial (August 2020–September 2021, five hospitals, 80 participants), patients received placebo, 0.3% NuGel, or 0.5% NuGel twice daily for four weeks.ResultsNuGel (0.3% [Nu0.3] and 0.5% [Nu0.5]) was well-tolerated, with no adverse drug reactions or serious adverse events. Nu0.3 showed a significant decrease in EASI score from baseline (-12.2%, [-30.3%, 5.9%], p = 0.04). Treatment with Nu0.5 resulted in a numerically decreased EASI score (-11.9%, [-34.9%, 11.1%], p > 0.05), which is comparable with placebo group (-2.9%, [-21.5%, 15.6%], p > 0.05). No significant difference was observed between groups (p>0.05). Plasma proteomic analysis identified biomarkers associated with blood coagulation, complement activation, and cell adhesion as predictors of response to Nu0.5. Patients with baseline profiles characterized by K2C5high, ENTP6low, or CRKlow demonstrated significant clinical improvement when treated with Nu0.5 compared to the placebo group. Among these, the CRKlow subgroup, comprising 54.3% of the biomarker analysis set, showed a ΔEASI of -61.3% [-99.9, -22.8; p = 0.003] and a ΔIGA of -35.2% [-58.2, -12.1; p = 0.004] compared to the placebo group. The biomarker signature demonstrated high predictive accuracy (AUC = 0.92, p = 0.002). Logistic regression analysis revealed that the threshold of predicted probability derived from the baseline plasma level of K2C5 and ENTP6 successfully stratified 100% of participants who responded to Nu0.5 (ΔEASI from baseline ≤ -50%), whereas none (0%) in the placebo group responded (p = 0.035).ConclusionBaseline biomarkers, such as K2C5, ENTP6, and CRK, may serve as predictors of clinical improvement in AD patients treated with Nu0.5, highlighting the potential for personalized treatment strategies. Further research is required to validate these findings in larger patient cohorts.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04530643

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat

Search for top squark pair production using dilepton final states in pp collision data collected at root s=13TeV

A search is presented for supersymmetric partners of the top quark (top squarks) in final states with two oppositely charged leptons (electrons or muons), jets identified as originating from bquarks, and missing transverse momentum. The search uses data from proton-proton collisions at root s = 13 TeV collected with the CMS detector, corresponding to an integrated luminosity of 137 fb(-1). Hypothetical signal events are efficiently separated from the dominant top quark pair production background with requirements on the significance of the missing transverse momentum and on transverse mass variables. No significant deviation is observed from the expected background. Exclusion limits are set in the context of simplified supersymmetric models with pair-produced lightest top squarks. For top squarks decaying exclusively to a top quark and a lightest neutralino, lower limits are placed at 95% confidence level on the masses of the top squark and the neutralino up to 925 and 450 GeV, respectively. If the decay proceeds via an intermediate chargino, the corresponding lower limits on the mass of the lightest top squark are set up to 850 GeV for neutralino masses below 420 GeV. For top squarks undergoing a cascade decay through charginos and sleptons, the mass limits reach up to 1.4 TeV and 900 GeV respectively for the top squark and the lightest neutralino.Peer reviewe

Measurement of the W gamma Production Cross Section in Proton-Proton Collisions at root s=13 TeV and Constraints on Effective Field Theory Coefficients

A fiducial cross section for W gamma production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb(-1) of data collected using the CMS detector at the LHC. The W -> e nu and mu nu decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.Peer reviewe

Observation of γγ → ττ in proton-proton collisions and limits on the anomalous electromagnetic moments of the τ lepton

The production of a pair of τ leptons via photon–photon fusion, γγ → ττ, is observed for the f irst time in proton–proton collisions, with a significance of 5.3 standard deviations. This observation is based on a data set recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138 fb−1. Events with a pair of τ leptons produced via photon–photon fusion are selected by requiring them to be back-to-back in the azimuthal direction and to have a minimum number of charged hadrons associated with their production vertex. The τ leptons are reconstructed in their leptonic and hadronic decay modes. The measured fiducial cross section of γγ → ττ is σfid obs = 12.4+3.8 −3.1 fb. Constraints are set on the contributions to the anomalous magnetic moment (aτ) and electric dipole moments (dτ) of the τ lepton originating from potential effects of new physics on the γττ vertex: aτ = 0.0009+0.0032 −0.0031 and |dτ| < 2.9×10−17ecm (95% confidence level), consistent with the standard model