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.
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.
We compared risks of clinical outcomes, mortality and healthcare costs among new users of different classes of anti-diabetic medications. This is a population-based, retrospective, new-user design ...cohort study using the Taiwan National Health Insurance Database between May 2, 2015 and September 30, 2017. An individual was assigned to a medication group based on the first anti-diabetic prescription on or after May 1, 2016: SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists or older agents (metformin, etc.). Clinical outcomes included lower extremity amputation, peripheral vascular disease, critical limb ischemia, osteomyelitis, and ulcer. We built three Cox proportional hazards models for clinical outcomes and mortality, and three regression models with a log-link function and gamma distribution for healthcare costs, all with propensity-score weighting and covariates. We identified 1,222,436 eligible individuals. After adjustment, new users of SGLT-2 inhibitors were associated with 73% lower mortality compared to those of DPP-4 inhibitors or users of older agents, while 36% lower total costs against those of GLP-1 agonists. However, there was no statistically significant difference in the risk of lower extremity amputation across medication groups. Our study suggested that SGLT-2 inhibitors is associated with lower mortality compared to DPP 4 inhibitors and lower costs compared to GLP-1 agonists.
We set out in this study to examine (a) whether “socially responsible investment” (SRI) portfolios can outperform less‐SRI portfolios in the emerging Asian stock markets and (b) whether investors ...within these emerging markets achieve awareness of SRI through publicly available news. On the basis of 2009–2013 data, we find that SRI portfolios tend to perform better in Japan. However, firms in the emerging Asian markets do not earn rewards for superior corporate social responsibility (CSR) practices. We also find that investors in the emerging Asian markets are indeed aware of SRI through public CSR news releases; in particular, investors in these markets reward high environmental‐, social‐, and governance‐rated firms for their good CSR practices advertised through such news releases, relative to those with no news releases.
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.
Angiopoietin‐like protein 1 (ANGPTL1) has been shown to act as a tumor suppressor by inhibiting angiogenesis, cancer invasion, and metastasis. However, little is known about the effects of ANGPTL1 on ...sorafenib resistance and cancer stem cell properties in hepatocellular carcinoma (HCC) and the mechanism underlying these effects. Here, we show that ANGPTL1 expression positively correlates with sorafenib sensitivity in HCC cells and human HCC tissues. ANGPTL1 significantly decreases epithelial‐mesenchymal transition (EMT)‐driven sorafenib resistance, cancer stemness, and tumor growth of HCC cells by repressing Slug expression. ANGPTL1 directly interacts with and inactivates MET receptor, which contributes to Slug suppression through inhibition of the extracellular receptor kinase/protein kinase B (ERK/AKT)‐dependent early growth response protein 1 (Egr‐1) pathway. ANGPTL1 expression inversely correlates with Slug expression, poor sorafenib responsiveness, and poor clinical outcomes in HCC patients. Conclusion: ANGPTL1 inhibits sorafenib resistance and cancer stemness in HCC cells by repressing EMT through inhibition of the MET receptor−AKT/ERK−Egr‐1−Slug signaling cascade. ANGPTL1 may serve as a novel MET receptor inhibitor for advanced HCC therapy. (Hepatology 2016;64:1637‐1651)
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Limited histopathology studies have suggested that reversible cerebral vasoconstriction syndromes (RCVS) does not present with vascular wall inflammation. Previous vascular imaging studies ...have had inconsistent vascular wall enhancement findings in RCVS patients. The aim of this study was to determine whether absence of arterial wall pathology on imaging is a universal finding in patients with RCVS.
Methods
We recruited patients with RCVS from Taipei Veterans General Hospital prospectively from 2010 to 2012, with follow-up until 2017 (
n
= 48). We analyzed the characteristics of vascular wall enhancement in these patients without comparisons to a control group. All participants received vascular wall imaging by contrasted T1 fluid-attenuated inversion recovery with a 3-T magnetic resonance machine. The vascular wall enhancement was rated as marked, mild or absent.
Results
Of 48 patients with RCVS, 22 (45.8%) had vascular wall enhancement (5 marked and 17 mild). Demographics, clinical profiles, and cerebral artery flow velocities were similar across patients with versus without vascular wall enhancement, except that patients with vascular wall enhancement had fewer headache attacks than those without (
p
= 0.04). Follow-up imaging completed in 14 patients (median interval, 7 months) showed reduced enhancement in 9 patients, but persistent enhancement in 5.
Conclusion
Almost half of our RCVS patients exhibited imaging enhancement of diseased vessels, and it was persistent for approximately a third of those patients with follow-up imaging. Both acute and persistent vascular wall enhancement may be unhelpful for differentiating RCVS from central nervous system vasculitis or subclinical atherosclerosis.
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.
Urologic cancer in Taiwan Hung, Chi-Feng; Yang, Cheng-Kuang; Ou, Yen-Chuan
Japanese journal of clinical oncology
46, Številka:
7
Journal Article
Recenzirano
Odprti dostop
For the past three decades, cancer is the number one cause of death in Taiwan. An increasing trend in the incidence of urologic cancers has also been noticed since 1979. In 2012, urologic cancer ...accounted for 10.0% of all the new malignant cases. Prostate, bladder and kidney cancers are the most common types. Metastatic prostate cancer still accounted for nearly 30% of new cases in Taiwan between 2004 and 2012. There are several specifically noticeable characteristics of urothelial carcinoma in Taiwan, associated with arseniasis and aristolochic acid. The diagnosis and treatment of urologic cancer mainly follows the current international guidelines. The development of minimal invasive surgery, especially DaVinci robotic surgical system, has made a marked change in the surgical treatment of urologic cancer. Meanwhile, newer systemic agents also commence and improve our standard of care. However, treatment decisions are greatly influenced by the National Health Insurance coverage. The current national cancer registry system should be renovated more comprehensively in order to gain better insight into specific features of urologic cancer in Taiwan.
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