The Roles of Lipoprotein in Psoriasis Shih, Chun-Ming; Chen, Chang-Cyuan; Chu, Chen-Kuo ...
International journal of molecular sciences,
01/2020, Letnik:
21, Številka:
3
Journal Article
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The association between psoriasis and cardiovascular disease risk has been supported by recent epidemiological data. Patients with psoriasis have an increased adjusted relative risk for myocardial ...infarction. As such, the cardiovascular risk conferred by severe psoriasis may be comparable to what is seen with other well-established risk factors, such as diabetes mellitus. Previous studies demonstrated that low-density lipoprotein (LDL) plays critical roles during atherogenesis. It may be caused by the accumulation of macrophages and lipoprotein in the vessel wall. Oxidized LDL (ox-LDL) stimulates the expression of adhesion molecules, such as ICAM-1 and VCAM-1, on endothelial cells and increases the attachment of mononuclear cells and the endothelium. Even though previous evidence demonstrated that psoriasis patients have tortuous and dilated blood vessels in the dermis, which results in the leakage of ox-LDL, the leaked ox-LDL may increase the expression of adhesion molecules and cytokines, and disturb the static balance of osmosis. Therefore, exploration of the relationship between hyperlipidemia and psoriasis may be another novel treatment option for psoriasis and may represent the most promising strategy.
Skin is an important organ that mainly functions as a barrier. Skin diseases can damage a person's self-confidence and reduce their willingness to socialize, as well as their social behavior and ...willingness. When the skin appearance is abnormal, in addition to affecting the quality of life, it often leads to personal, social, and psychological dysfunction and even induces depression. Psoriasis and atopic dermatitis are common chronic skin diseases. Their prevalence in the world is 3-10%, and there is an increasing trend year by year. These congenital or acquired factors cause the dysfunction of the immune system and then destroy the barrier function of the skin. Because these patients are flooded with a variety of inflammatory mediators, this causes skin cells to be in chronic inflammation. Therefore, psoriasis and atopic dermatitis are also considered systemic chronic inflammatory diseases. In the healthcare systems of developed countries, it is unavoidable to spend high costs to relieve symptoms of psoriasis and atopic dermatitis patients, because psoriasis and atopic dermatitis have a great influence on individuals and society. Giving a lot of attention and developing effective treatment methods are the topics that the medical community must work on together. Therefore, we used a narrative review manuscript to discuss pathogenesis, clinical classification, incidence, and treatment options, including topical medication, systemic therapeutics, immunosuppressive medication for psoriasis, and atopic dermatitis, as well as also comparing the differences between these two diseases. We look forward to providing readers with comprehensive information on psoriasis and atopic dermatitis through this review article.
TDP-43 is a pathogenic protein: its normal function in binding to UG-rich RNA is related to cystic fibrosis, and inclusion of its C-terminal fragments in brain cells is directly linked to ...frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Here we report the 1.65 Å crystal structure of the C-terminal RRM2 domain of TDP-43 in complex with a single-stranded DNA. We show that TDP-43 is a dimeric protein with two RRM domains, both involved in DNA and RNA binding. The crystal structure reveals the basis of TDP-43's TG/UG preference in nucleic acids binding. It also reveals that RRM2 domain has an atypical RRM-fold with an additional β-strand involved in making protein–protein interactions. This self association of RRM2 domains produced thermal-stable RRM2 assemblies with a melting point greater than 85°C as monitored by circular dichroism at physiological conditions. These studies thus characterize the recognition between TDP-43 and nucleic acids and the mode of RRM2 self association, and provide molecular models for understanding the role of TDP-43 in cystic fibrosis and the neurodegenerative diseases related to TDP-43 proteinopathy.
Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the drug hypersensitivity syndrome, ...Stevens-Johnson syndrome, and toxic epidermal necrolysis. The adverse events are unpredictable and carry significant morbidity and mortality. To identify genetic markers for allopurinol-SCAR, we carried out a case-control association study. We enrolled 51 patients with allopurinol-SCAR and 228 control individuals (135 allopurinol-tolerant subjects and 93 healthy subjects from the general population), and genotyped for 823 SNPs in genes related to drug metabolism and immune response. The initial screen revealed strong association between allopurinol-SCAR and SNPs in the MHC region, including BAT3 (encoding HLA-B associated transcript 3), MSH5 (mutS homolog 5), and MICB (MHC class I polypeptide-related sequence B) ($P<10^{-7}$). We then determined the alleles of HLA loci A, B, C, and DRB1. The HLA-B*5801 allele was present in all (100%) 51 patients with allopurinol-SCAR, but only in 20 (15%) of 135 tolerant patients odds ratio 580.3 (95% confidence interval, 34.4-9780.9); corrected P value=4.7× 10-24 and in 19 (20%) of 93 of healthy subjects 393.51 (23.23-6665.26); corrected P value=8.1× 10-18. HLA alleles A*3303, Cw*0302, and DRB1*0301 were in linkage disequilibrium and formed an extended haplotype with HLA-B*5801. Our results indicated that allopurinol-SCAR is strongly associated with a genetic predisposition in Han Chinese. In particular, HLA-B*5801 allele is an important genetic risk factor for this life-threatening condition.
The etiology of chronic urticaria (CU) is diverse, with chronic infections and inflammation being reported as considerable contributing factors. Although the prevalence of metabolic syndrome was ...found to be significantly elevated in patients with CU, no one has specifically estimated the effects on CU following hyperlipidemia. This study aimed to examine the association between hyperlipidemia and CU using a population-based dataset in Taiwan. This study included 9798 adults with CU as cases and 9798 sex- and age-matched controls. These patients were examined for whether they had received a prior diagnosis of hyperlipidemia. We used conditional logistic regression analyses to calculate the odds ratio (OR) and its corresponding 95% confidence interval (CI) for having been previously diagnosed with hyperlipidemia between cases and controls. In total, 7066 (36.1%) patients had received a prior diagnosis of hyperlipidemia, including 4287 (43.8%) among CU cases and 2779 (28.4%) among controls. The conditional logistic regression revealed that the OR of prior hyperlipidemia for cases was 1.97 (95% CI: 1.85~2.09) compared to the controls. Furthermore, compared to patients without CU, patients with CU independently experienced a 1.65-fold (95% CI = 1.55~1.76; p<0.001) increased risk of having a prior hyperlipidemia diagnosis, after adjustments were made. We concluded that CU was associated with having received a prior diagnosis of hyperlipidemia.
A gas chromatography coupled with tandem mass spectrometry (GC-MS/MS) method is developed to determine 18 representative polycyclic aromatic hydrocarbons (PAHs) in cosmetics, including Benzoapyrene ...(BaP) and others. The method offers high sensitivity and selectivity under selected reaction monitoring (SRM) mode to satisfy the requirements of both quantitation and qualitation. The extraction solvent system used in this study is acetone/hexane 1:1 (v/v) and other purification procedure is unnecessary. The linearities of 18 PAHs are validated in different concentration in the range of 0.25–20 ng/mL individually with coefficient correlation (r) higher than 0.996. The recoveries for spiking 3 different concentrations are from 87.40% to 120.44% for 18 PAHs and the coefficient of variation (CV) are below 12.32%. Limit of quantification (LOQ) of 18 PAHs is in the range of 0.05–0.2 mg/kg. A matrix enhancement effect is observed and can be compensated with deuterated internal standard. The method has been successfully applied to 73 samples, over 40 of them are lipsticks. The results show none of the samples detect Benzoapyrene (BaP) and Dibenzoa,hanthracene (DBA), both are classified as the most carcinogenic. 8 PAHs are detected and the average value between 0.08 and 0.27 mg/kg. This study offers a sensitive and simple method to analyze 18 representative PAHs successfully and can be applied to cosmetic products and raw materials.
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•This article develop a method to analyze 18 PAHs by GC-MS/MS under selected reaction monitoring (SRM) mode.•The sample preparation is simple by acetone/hexane 1:1 (v/v) extraction. The LOQs for 18 PAHs range from 0.05 to 0.2 mg/kg.•Apply the method to 73 samples and 8 PAHs in trace amount are detected with the average value between 0.08 and 0.27 mg/kg.
Because tyrosinase catalyzes melanin synthesis, tyrosinase inhibitors are important in cosmetic skin-whitening. Oxidative stress contributes to skin aging and can adversely affect skin health, which ...means antioxidants active in skin cells may support skin health. We examined 25 traditional Chinese herbal medicines that might be useful for skin-whitening and skin health. Extracts (100
μg/mL) were tested for cytotoxicity on human epidermal melanocytes (HEMn); 12 exhibited low cytotoxicity. Their effects on tyrosinase and melanin inhibitory activities and free radical scavenging activities were further assessed. Phenolic contents were evaluated using Folin–Ciocalteu reagent. Four herbs,
Pharbitis nil,
Sophora japonica,
Spatholobus suberectus, and
Morus alba, exhibited potent inhibitory effects on tyrosinase (IC
50 values 24.9, 95.6, 83.9, and 78.3
μg/mL, respectively). Melanin inhibition was not dose-dependent.
Sophora japonica (IC
50: 14.46
μg/mL, 1,1-diphenyl-2-picrylhydrazyl (DPPH); 1.95
μg/mL, hydroxyl radical) and
Spatholobus suberectus (IC
50: 10.51
μg/mL, DPPH; 4.36
μg/mL, hydroxyl radical) showed good antioxidative activities and high phenolic contents (255 and 189
mg of gallic acid/g extract, respectively). Among active anti-tyrosinase extracts,
Sophora japonica and
Spatholobus suberectus were especially potent in HEMn cells in terms of free radical scavenging effects and high phenolic contents, making them the strongest candidates for cosmetic application found in the current study.
Life does not sustain without water. For water, there is a natural abundance of stable isotope hydrogen and oxygen. Water molecules get across cell membranes through a plasma membrane protein, named ...aquaporin. Moreover, the kidney is the main organ to maintain water homeostasis. Here, we study the stable isotopic ratios of hydrogen and oxygen in human blood plasma and erythrocyte corresponding to kidney functions. We extract waters from human plasma and erythrocyte, collected from 110 participants, including 51 clinically stable outpatients with end‐stage renal disease (ESRD) and 59 subjects with normal renal function (NRF). We observed that (i) both extracellular (blood plasma) and intracellular (erythrocyte) biology waters are isotopic differences between the ESRD and NRF participants, (ii) the natural abundance of isotopic waters of ESRD is hypo‐isotopic, and (iii) the isotopic enrichment of water between erythrocyte and blood plasma are distinct. In addition, we introduce an empirical formula using entropy transformation to describe isotopic water enrichment for biology. Accordingly, the natural abundance of stable isotope water of blood plasma and erythrocyte may be possibly put in practice a new sign for assessments of kidney dysfunctions.
The claustrum (CLA) is a conspicuous subcortical structure interconnected with cortical and subcortical regions. Its regional anatomy and cell-type-specific connections in the mouse remain not fully ...determined. Using multimodal reference datasets, we confirmed the delineation of the mouse CLA as a single group of neurons embedded in the agranular insular cortex. We quantitatively investigated brain-wide inputs and outputs of CLA using bulk anterograde and retrograde viral tracing data and single neuron tracing data. We found that the prefrontal module has more cell types projecting to the CLA than other cortical modules, with layer 5 IT neurons predominating. We found nine morphological types of CLA principal neurons that topographically innervate functionally linked cortical targets, preferentially the midline cortical areas, secondary motor area, and entorhinal area. Together, this study provides a detailed wiring diagram of the cell-type-specific connections of the mouse CLA, laying a foundation for studying its functions at the cellular level.
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•The prefrontal module sends stronger input to CLA than the other 5 cortical modules•The claustrum receives stronger input from L5 IT neurons than from other cell types•The claustrum receives inputs from 31 subcortical structures•Nine types of claustrum principal neurons innervate diverse cortical targets
The claustrum is a subcortical structure interconnected with cortical and subcortical regions and its cellular anatomy remains not fully resolved. Wang et al. show regional and cell-type-specific inputs and outputs of the mouse claustrum. Its strong connections with the prefrontal module support the claustrum’s involvement in higher cognitive functions.
Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying ...mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of psoriasis and dyslipidemia is an important issue that may lead to the development of effective therapies. Under this principle, we investigated the influences of hyperlipidemia in imiquimod (IMQ)-induced psoriasis-like B6.129S2-
/J mice and oxidized low-density lipoprotein (oxLDL) in tumor necrosis factor (TNF)-α-stimulated Hacat cells. In our study, we showed that a high-cholesterol diet aggravated psoriasis-like phenomena in IMQ-treated B6.129S2-
/J mice. In vitro analysis showed that oxLDL increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. High-cholesterol diet aggravated IL-23 expression in IMQ-treated B6.129S2-
/J mice, and oxLDL induced IL-23 expression mediated by LOX-1 in TNF-α-stimulated Hacat cells. Therefore, it will be interesting to investigate the factors for the oxLDL induction of LOX-1 in psoriasis. LOX-1 receptor expression may be another novel treatment option for psoriasis and might represent the most promising strategy.
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