• Waters From posted an update 3 days, 9 hours ago

    Our study demonstrates that mutated NRAS cooperates with NUP98-NSD1 and shows that direct targeting of the fusion can be exploited as a novel treatment strategy in NUP98-NSD1-positive AML patients.Origanum L. (Lamiaceae) is an important genus of medicinal and aromatic plants used in traditional medicine since ancient times as culinary herbs and remedies. The aim of the present study was to evaluate the chemical composition, as well as the biochemical and cellular activities of freshly prepared Origanum majorana L. essential oil (OmEO) in an Alzheimer’s disease (AD) amyloid beta1-42 (Aβ1-42) rat model. OmEO (1% and 3%) was inhaled for 21 consecutive days, while Aβ1-42 was administered intracerebroventricularly to induce AD-like symptoms. Our data demonstrate that OmEO increased antioxidant activity and enhanced brain-derived neurotrophic factor (BDNF) expression, which in concert contributed to the improvement of cognitive function of animals. Moreover, OmEO presented beneficial effects on memory performance in Y-maze and radial arm-maze tests in the Aβ1-42 rat AD model.Tractional retinal detachment (TRD) causes visual loss in diabetes mellitus patients. Silicone oil can be used as a tamponade to repair retinal detachment; however, intrasilicone injection is challenging. We aimed to evaluate the effect of intrasilicone bevacizumab injection in TRD surgery. This was a single-hospital, retrospective, case-control study of 44 patients (46 eyes). We reviewed medical histories and ophthalmic examination results. We administered silicone oil to 26 eyes (group I), and a combination of silicone oil and intravitreal bevacizumab injection to 20 eyes (group II). The main outcome measures were the logarithm of the minimum angle of resolution (logMAR) visual acuity and central macular thickness. Mean change in logMAR visual acuity was larger (p = 0.029) in group II (-0.99 ± 0.73) than in group I (-0.56 ± 0.80), 12 months postoperatively. Compared to group I, group II exhibited a lower mean (471.54 ± 120.14 μm vs. 363.40 ± 59.57 µm, respectively; p = 0.001), and mean change (-22.39 ± 203.99 μm vs. -72.40 ± 139.35 µm, respectively; p = 0.027), in central macular thickness, 1 month postoperatively. Intrasilicone bevacizumab injection immediately after vitrectomy may rapidly reduce central macular thickness and increase final visual acuity. Prospective studies are necessary to demonstrate long-term safety and efficacy.The uneven surface of the weld seam makes eddy current testing more susceptible to the lift-off effect of the probe. Therefore, the defect of carbon steel plate welds has always been a difficult problem in eddy current testing. This study aimed to design a new type of eddy current orthogonal axial probe and establish the finite element simulation model of the probe. The effect of the probe structure, coil turns, and coil size on the detection sensitivity was simulated. Further, a designed orthogonal axial probe was used to conduct a systematic experiment on the weld of carbon steel specimens, and the 0.2 mm width and 1 mm depth of weld defects of carbon steel plates were effectively detected. The experimental results showed that the new orthogonal axial eddy current probe effectively suppressed the unevenness effect of the weld surface on the lift-off effect during the detection process.

    Multifocal motor neuropathy (MMN) is a rare inflammatory neuropathy, clinically characterized by exclusive motor involvement. We wished to evaluate the possible presence of sensory dysfunction, including the evaluation of small fibres, after a long-term disease course.

    seven MMN patients, regularly followed in our Neurology Department, underwent clinical evaluation, neurophysiological examination by nerve conduction studies (NCSs), and Sudoscan. We compared neurophysiological data with a group of patients with other disorders of the peripheral nervous system.

    NCSs showed a reduction of sensory nerve action potential amplitude in 2/7 MMN patients. compound library inhibitor Sudoscan showed borderline electrochemical skin conductance (ESC) values in 3/7 MMN patients (two of them with abnormal sensory NCSs).

    Our results confirm that sensory involvement may be found in some MMN after a long-term disease course, and it could also involve the small fibres.

    Our results confirm that sensory involvement may be found in some MMN after a long-term disease course, and it could also involve the small fibres.Scar formation can cause the failure of glaucoma filtration surgery. We investigated the effect of AR12286, a selective Rho-associated kinase inhibitor, on myofibroblast transdifferentiation and intraocular pressure assessment in rabbit glaucoma filtration surgery models. Cell migration and collagen contraction were used to demonstrate the functionality of AR12286-modulated human conjunctival fibroblasts (HConFs). Polymerase chain reaction quantitative analysis was used to determine the effect of AR12286 on the production of collagen Type 1A1 and fibronectin 1. Cell migration and collagen contraction in HConFs were activated by TGF-β1. However, compared with the control group, rabbit models treated with AR12286 exhibited higher reduction in intraocular pressure after filtration surgery, and decreased collagen levels at the wound site in vivo. Therefore, increased α-SMA expression in HConFs induced by TGF-β1 could be inhibited by AR12286, and the production of Type 1A1 collagen and fibronectin 1 in TGF-β1-treated HConFs was inhibited by AR12286. Overall, the stimulation of HConFs by TGF-β1 was alleviated by AR12286, and this effect was mediated by the downregulation of TGF-β receptor-related SMAD signaling pathways. In vivo results indicated that AR12286 thus improves the outcome of filtration surgery as a result of its antifibrotic action in the bleb tissue because AR12286 inhibited the TGF-β receptor-related signaling pathway, suppressing several downstream reactions in myofibroblast transdifferentiation.MiR-146a is upregulated in the stem cell-enriched limbal region vs. central human cornea and can mediate corneal epithelial wound healing. The aim of this study was to identify miR-146a targets in human primary limbal epithelial cells (LECs) using genomic and proteomic analyses. RNA-seq combined with quantitative proteomics based on multiplexed isobaric tandem mass tag labeling was performed in LECs transfected with miR-146a mimic vs. mimic control. Western blot and immunostaining were used to confirm the expression of some targeted genes/proteins. A total of 251 differentially expressed mRNAs and 163 proteins were identified. We found that miR-146a regulates the expression of multiple genes in different pathways, such as the Notch system. In LECs and organ-cultured corneas, miR-146a increased Notch-1 expression possibly by downregulating its inhibitor Numb, but decreased Notch-2. Integrated transcriptome and proteome analyses revealed the regulatory role of miR-146a in several other processes, including anchoring junctions, TNF-α, Hedgehog signaling, adherens junctions, TGF-β, mTORC2, and epidermal growth factor receptor (EGFR) signaling, which mediate wound healing, inflammation, and stem cell maintenance and differentiation.