Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical ...treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (Nelumbo nucifera). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The recent progress of efficiency improvement, emission color tuning, and lifetime elongation of blue organic light-emitting diodes (OLEDs) is reviewed. The latter is one of the most important ...bottlenecks for OLED development. The current status of blue light-emitting material design with emission mechanisms such as fluorescence (F), phosphorescence (Ph), thermally activated delayed fluorescence (TADF), and hybridized local and charge transfer (HLCT) is introduced in the first part of this review. Compared to red and green devices, the long exciton lifetime of the high energy triplet exciton in a blue OLED is the one of the main issues. To avoid the accumulation of high energy triplet excitons in the emitter for blue OLEDs, assisted triplet-triplet fluorescence (TTF) and Hyperfluorescence™ are employed to harvest the triplet excitons. In the second part of this review, we focus on issues from an application viewpoint: what are the requirements of blue OLEDs for display and lighting technologies in terms of efficiency, color, and lifetime? Key performance metrics of blue OLEDs with different technologies over time are summarized. Independent of technology, the trend is similar: the external quantum efficiency improves for the first stage of research, followed by color tuning, and then finally lifetime elongation. The state-of-the-art device performance of blue OLEDs with various emission mechanisms is illustrated. Although Ph- and TADF-emission based devices show satisfactory efficiency and electroluminescence (EL) spectra, despite having a lower efficiency TTF-emission based devices are the mainstream for real applications due to their relatively long operation lifetime. Blue Ph-OLEDs have the potential for lighting applications with suitable material selection and device design. We collected the published results and tried our best to make a fair comparison of the operation lifetime among different technologies. Finally, we discuss the possible future outlook from different viewpoints including new materials, device designs, and applications of blue OLEDs.
Emission mechanisms for OLEDs and their characteristics.
This study was undertaken to investigate migraine glymphatic and meningeal lymphatic vessel (mLV) functions.
Migraine patients and healthy controls (HCs) were prospectively recruited between 2020 and ...2023. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index for glymphatics and dynamic contrast-enhanced magnetic resonance imaging parameters (time to peak TTP/enhancement integral EI/mean time to enhance MTE) for para-superior sagittal (paraSSS)-mLV or paratransverse sinus (paraTS)-mLV in episodic migraine (EM), chronic migraine (CM), and CM with and without medication-overuse headache (MOH) were analyzed. DTI-ALPS correlations with clinical parameters (migraine severity numeric rating scale/disability Migraine Disability Assessment (MIDAS)/bodily pain Widespread Pain Index/sleep quality Pittsburgh Sleep Quality Index (PSQI)) were examined.
In total, 175 subjects (112 migraine + 63 HCs) were investigated. DTI-ALPS values were lower in CM (median interquartile range = 0.64 0.12) than in EM (0.71 0.13, p = 0.005) and HCs (0.71 0.09, p = 0.004). CM with MOH (0.63 0.07) had lower DTI-ALPS values than CM without MOH (0.73 0.12, p < 0.001). Furthermore, CM had longer TTP (paraSSS-mLV: 55.8 12.9 vs 40.0 7.6, p < 0.001; paraTS-mLV: 51.2 8.1 vs 44.0 3.3, p = 0.002), EI (paraSSS-mLV: 45.5 42.0 vs 16.1 9.2, p < 0.001), and MTE (paraSSS-mLV: 253.7 6.7 vs 248.4 13.8, p < 0.001; paraTS-mLV: 252.0 6.2 vs 249.7 1.2, p < 0.001) than EM patients. The MIDAS (p = 0.002) and PSQI (p = 0.002) were negatively correlated with DTI-ALPS index after Bonferroni corrections (p < q = 0.01).
CM patients, particularly those with MOH, have glymphatic and meningeal lymphatic dysfunctions, which are highly clinically relevant and may implicate pathogenesis for migraine chronification. ANN NEUROL 2024;95:583-595.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Gold has always been regarded as a symbol of nobility, and its shiny golden appearance has always attracted the attention of many people. Gold has good ductility, molecular recognition properties, ...and good biocompatibility. At present, gold is being used in many fields. When gold particles are as small as several nanometers, their physical and chemical properties vary with their size in nanometers. The surface area of a nano-sized gold surface has a special effect. Therefore, gold nanoparticles can, directly and indirectly, give rise to different biological activities. For example, if the surface of the gold is sulfided. Various substances have a strong chemical reactivity and are easy to combine with sulfhydryl groups; hence, nanogold is often used in biomedical testing, disease diagnosis, and gene detection. Nanogold is easy to bind to proteins, such as antibodies, enzymes, or cytokines. In fact, scientists use nanogold to bind special antibodies, as a tool for targeting cancer cells. Gold nanoparticles are also directly cytotoxic to cancer cells. For diseases caused by inflammation and oxidative damage, gold nanoparticles also have antioxidant and anti-inflammatory effects. Based on these unique properties, gold nanoparticles have become the most widely studied metal nanomaterials. Many recent studies have further demonstrated that gold nanoparticles are beneficial for humans, due to their functional pharmacological properties in a variety of diseases. The content of this review will be the application of gold nanoparticles in treating or diagnosing pressing diseases, such as cancers, retinopathy, neurological diseases, skin disorders, bowel diseases, bone cartilage disorders, cardiovascular diseases, infections, and metabolic syndrome. Gold nanoparticles have shown very obvious therapeutic and application potential.
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Psoriasis is a common non-contagious chronic inflammatory skin lesion, with frequent recurrence. It mainly occurs due to aberrant regulation of the immune system leading to abnormal proliferation of ...skin cells. However, the pathogenic mechanisms of psoriasis are not fully understood. Although most of the current therapies are mostly efficient, the side effects can result in therapy stop, which makes the effectiveness of treatment strategies limited. Therefore, it is urgent and necessary to develop novel therapeutics. Here, we investigated the efficacy of chrysin, a plant flavonoid, which we previously reported to possess strong antioxidant and anti-inflammatory effects, against psoriasis-like inflammation. Our results revealed that chrysin significantly attenuated imiquimod-induced psoriasis-like skin lesions in mice, and improved imiquimod-induced disruption of skin barrier. Moreover, the TNF-α, IL-17A, and IL-22-induced phosphorylation of MAPK and JAK-STAT pathways, and activation of the NF-κB pathway were also attenuated by chrysin pretreatment of epidermal keratinocytes. Most importantly, chrysin reduced TNF-α-, IL-17A-, and IL-22-induced CCL20 and antimicrobial peptide release from epidermal keratinocytes. Thus, our findings indicate that chrysin may have therapeutic potential against inflammatory skin diseases. Our study provides a basis for further investigating chrysin as a novel pharmacologic agent and contributes to the academic advancement in the field of Chinese herbal medicine.
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UV irradiation can injure the epidermis, resulting in sunburn, inflammation, and cutaneous tissue disorders. Previous studies demonstrate that EGFR in keratinocytes can be activated by UVB and ...contributes to inflammation. Poly (ADP‐ribose) polymerase‐1 (PARP‐1) is a nuclear enzyme and plays an essential role in DNA repair under moderate stress. In this study, we set out to understand how PARP‐1 regulates UVB irradiation‐induced skin injury and interplays with EGFR to mediate the inflammation response. We found that PARP‐1 deficiency exacerbated the UVB‐induced inflammation, water loss, and back skin damage in mice. In human primary keratinocytes, UVB can activate PARP‐1 and enhance DNA damage upon PARP‐1 gene silencing. Moreover, PARP‐1 silencing and PARP inhibitor olaparib can suppress UVB‐induced COX‐2 and MMP‐1 expression, but enhance TNF‐α and IL‐8 expression. In addition, EGFR silencing or EGFR inhibition by gefitinib can decrease UVB‐induced COX‐2, TNF‐α, and IL‐8 expression, suggesting EGFR activation via paracrine action can mediate UVB‐induced inflammation responses. Immunoblotting data revealed that PARP‐1 inhibition decreases UVB‐induced EGFR and p38 activation. Pharmacological inhibition of p38 also dramatically led to the attenuation of UVB‐induced inflammatory gene expression. Of note, genetic ablation of PARP‐1 or EGFR can attenuate UVB‐induced ROS production, and antioxidant NAC can attenuate UVB‐induced EGFR‐p38 signaling axis and PARP‐1 activation. These data suggest the regulatory loops among EGFR, PARP‐1, and ROS upon UVB stress. PARP‐1 not only serves DNA repair function but also orchestrates interactions to EGFR transactivation and ROS production, leading to p38 signaling for inflammatory gene expression in keratinocytes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is originally featured with a strong clustering of mutations in NOTCH3 exons 3-6 and ...leukoencephalopathy with frequent anterior temporal pole involvement. The present study aims at characterizing the genotypic and phenotypic profiles of CADASIL in Taiwan. One hundred and twelve patients with CADASIL from 95 families of Chinese descents in Taiwan were identified by Sanger sequencing of exons 2 to 24 of NOTCH3. Twenty different mutations in NOTCH3 were uncovered, including 3 novel ones, and R544C in exon 11 was the most common mutation, accounting for 70.5% of the pedigrees. Haplotype analyses were conducted in 14 families harboring NOTCH3 R544C mutation and demonstrated a common haplotype linked to NOTCH3 R544C at loci D19S929 and D19S411. Comparing with CADASIL in most Caucasian populations, CADASIL in Taiwan has several distinct features, including less frequent anterior temporal involvement, older age at symptom onset, higher incidence of intracerebral hemorrhage, and rarer occurrence of migraine. Subgroup analyses revealed that the R544C mutation is associated with lower frequency of anterior temporal involvement, later age at onset and higher frequency of cognitive dysfunction. In conclusion, the present study broadens the spectrum of NOTCH3 mutations and provides additional insights for the clinical and molecular characteristics of CADASIL patients of Han-Chinese descents.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Liquid crystals have great potential for developing photonic devices that control the optical behaviors of liquid crystals in smart devices with external stimulation. In this study, we have ...demonstrated a series of bistable cholesteric liquid crystal devices using the dual-frequency nematic liquid crystal HEF951 assisted by a predesigned chiral ferroelectric liquid crystal. The synthesized chiral ferroelectric liquid crystal was used to induce the formation of the cholesteric liquid crystal phase and decrease the driving voltages and response times of the fabricated bistable liquid crystal devices. The fabricated ferroelectric liquid crystal-assisted bistable cholesteric liquid crystal devices showed a stable opaque focal conic state and stable transparent planar state without any energy consumption once they were turned "from focal-conic to planar" and "from planar to focal-conic". To enhance the reliability, the fabricated bistable cholesteric liquid crystal devices were further stabilized by polymer matrixes. Switching of the bistable liquid crystal cells from one state to another was achieved by a one-step voltage bias with various frequencies. Furthermore, the response time of the sample cell was calculated as 1.7 ms. These results suggest that fabricated ferroelectric liquid crystal-assisted bistable cholesteric liquid crystal devices can be applied to produce energy-saving green liquid crystal displays and other related smart devices.
Fabricated polymer-stabilized bistable cholesteric liquid crystal devices show a stable opaque focal conic state and a stable transparent planar state without any energy consumption once they are turned.
In this prospective study, Han Chinese subjects who were candidates for carbamazepine therapy were screened for the HLA-B*1502 allele because of its association with the Stevens–Johnson syndrome and ...toxic epidermal necrolysis.
The Stevens–Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), are two of the most serious adverse reactions caused by drugs. SJS is characterized by high fever, malaise, and a rapidly developing, blistering exanthema of macular papules and target-like lesions, accompanied by mucosal involvement. This condition is associated with a rate of death of approximately 5%. TEN has a similar presentation, with even more extensive skin detachment and a death rate of 25 to 35%.
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Carbamazepine, an anticonvulsant and specific analgesic agent for trigeminal neuralgia, is the most common cause of SJS–TEN in Southeast Asian countries.
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We previously . . .
Mast cells play a very important role in skin allergy and inflammation, including atopic dermatitis and psoriasis. In the past, it was found that neferine has anti-inflammatory and anti-aging effects ...on the skin, but its effect on mast cells has not yet been studied in detail. In this study, we used mast cells (RBL-2H3 cells) and mouse models to study the anti-allergic and inflammatory effects of neferine. First, we found that neferine inhibits the degranulation of mast cells and the expression of cytokines. In addition, we observed that when mast cells were stimulated by A23187/phorbol 12-myristate-13-acetate (PMA), the elevation of intracellular calcium was inhibited by neferine. The phosphorylation of the MAPK/NF-κB pathway is also reduced by pretreatment of neferine. The results of in vivo studies show that neferine can improve the appearance of dermatitis and mast cell infiltration caused by dinitrochlorobenzene (DNCB). Moreover, the expressions of barrier proteins in the skin are also restored. Finally, it was found that neferine can reduce the scratching behavior caused by compound 48/80. Taken together, our results indicate that neferine is a very good anti-allergic and anti-inflammatory natural product. Its effect on mast cells contributes to its pharmacological mechanism.
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