scholarly journals Smoking and Skin Diseases: A Crucial Causal Link

2014 ◽  
Vol 41 (2) ◽  
pp. 61-63 ◽  
Author(s):  
N Ahmed ◽  
MZ Islam
Keyword(s):  
Tobacco Smoking ◽  
Lupus Erythematosus ◽  
Chronic Wounds ◽  
Cell Function ◽  
Skin Diseases ◽  
Health Hazard ◽  
Pemphigus Vulgaris ◽  
Causal Link ◽  
Etiologic Factor ◽  
Protective Effects

Tobacco smoking is a serious and preventable health hazard that can cause or exacerbate a number of diseases and shorten life expectancy, but the role of smoking as an etiologic factor in the development of skin disease is largely unknown. Although epidemiological evidence is sparse, findings suggest that tobacco smoking is a contributing factor in systemic lupus erythematosus, psoriasis, palmoplantar pustulosis, cutaneous squamous cell carcinoma, hidradenitis suppurativa, and genital warts. In contrast, smoking may confer some protective effects and mitigate other skin diseases, notably pemphigus vulgaris, pyoderma gangrenosum, aphthous ulcers, and Behçet's disease. Various degenerative dermatologic conditions are also impacted by smoking, such as skin wrinkling and dysregulated wound healing, which can result in post-surgical complications and delayed or even arrested healing of chronic wounds. Most likely, alteration of inflammatory cell function and extracellular matrix turnover caused by smoking-induced oxidative stress are involved in the pathophysiologic mechanisms. DOI: http://dx.doi.org/10.3329/bmj.v41i2.18813 Bangladesh Medical Journal 2012 Vol. 41 No. 2: 61-63

The Comparative Pathology of Non-Viral Bullous Skin Diseases in Domestic Animals

1980 ◽  
Vol 17 (3) ◽  
pp. 257-281 ◽  
Author(s):  
D. W. Scott ◽  
M. J. Wolfe ◽  
C. A. Smith ◽  
R. M. Lewis
Keyword(s):  
New York ◽  
Epidermolysis Bullosa ◽  
Lupus Erythematosus ◽  
Skin Diseases ◽  
New York State ◽  
Pemphigus Vulgaris ◽  
Domestic Animals ◽  
Pemphigus Foliaceus ◽  
Epidermolysis Bullosa Simplex ◽  
Bullous Skin Diseases

In a review of non-viral bullous skin diseases of domestic animals and a 4-year study of cases presented to the New York State College of Veterinary Medicine, we found 15 diseases: pemphigus vulgaris, pemphigus vegetans, pemphigus foliaceus, pemphigus erythematosus, bullous pemphigoid, systemic lupus erythematosus, dermatitis herpetiformis, toxic epidermal necrolysis, drug eruption, epidermolysis bullosa, epidermolysis bullosa simplex, familial acantholysis, bovine congenital porphyria, impetigo and subcorneal pustular dermatosis. The 15 diseases were placed in five categories: autoimmune, immune-mediated, hereditary, bacterial and idiopathic. A histologic classification of these disorders based on the site of blister formation and other important clinicopathologic, histologic and immunopathologic findings was developed.

scholarly journals 2456 Cutaneous lupus erythematosus patients have increased circulating myeloid-derived suppressor cells with immunosuppressive properties

2018 ◽  
Vol 2 (S1) ◽  
pp. 7-8
Author(s):  
Stephanie Florez-Pollack ◽  
Lin-chiang Tseng ◽  
Masato Kobayashi ◽  
Benjamin F. Chong ◽  
Kiyoshi Ariizumi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Cell Function ◽  
Skin Diseases ◽  
Cutaneous Lupus Erythematosus ◽  
Dependent Manner ◽  
Activated T Cells ◽  
T Cell Function ◽  
Cutaneous Lupus

OBJECTIVES/SPECIFIC AIMS: MDSCs are potent suppressors of T cell function, and have been recently found to be implicated in skin diseases driven by T cell dysregulation. However, the function of MDSCs in CLE is poorly understood. We sought to characterize the MDSC population in the peripheral blood of DLE patients and evaluate their ability to suppress autologous T cells. METHODS/STUDY POPULATION: All patients were recruited through the UT Southwestern Cutaneous Lupus Registry. PBMCs from 32 CLE patients and 16 age-matched and gender-matched controls were analyzed using flow cytometry. Monocytic MDSCs were identified by the phenotype of CD14+ HLA-DR neg/low. Furthermore, autologous MDSCs and T cells were purified from CLE PBMCs (n=4) and co-cultured at different ratios of these cells. T cell function was measured by secretion of IFN-γ by ELISA. RESULTS/ANTICIPATED RESULTS: Monocytic MDSCs in CLE PBMCs (median: 2.04%, IQR: 0.67%–5.07%) were significantly higher compared with healthy control PBMCs (median: 0.5%, IQR: 0.1%–1.07%, p=0.002). Although not significant on subset analysis, patients with CLE limited to the head and neck had the highest levels of MDSCs. CLE MDSCs (n=4) were found to suppress autologous activated T-cells in a dose-dependent manner. DISCUSSION/SIGNIFICANCE OF IMPACT: In this cross-sectional study of patients of the UT Southwestern Cutaneous Lupus Registry, we observed differences in the levels of MDSCs among PBMCs of CLE patients Versus healthy controls. CLE patients had significantly higher levels of MDSCs, which could be explained by the presence of an inflammatory state in this group. Furthermore, CLE MDSCs were able to suppress autologous T cells, showing that these cells are functionally patent in CLE blood. Their up-regulation in CLE blood may represent the body’s response to limiting disease severity, since most patients had mild disease activity.

scholarly journals Extracellular Vesicles as Potential Theranostic Platforms for Skin Diseases and Aging

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 760
Author(s):  
Hyosuk Kim ◽  
Jong Won Lee ◽  
Geonhee Han ◽  
Kwangmeyung Kim ◽  
Yoosoo Yang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Extracellular Vesicles ◽  
Lupus Erythematosus ◽  
Chronic Wounds ◽  
Skin Diseases ◽  
Skin Aging ◽  
Therapeutic Agents ◽  
Systemic Lupus ◽  
Theranostic Agents

Extracellular vesicles (EVs), naturally secreted by cells, act as mediators for communication between cells. They are transported to the recipient cells along with cargoes such as nucleic acids, proteins, and lipids that reflect the changes occurring within the parent cells. Thus, EVs have been recognized as potential theranostic agents for diagnosis, treatment, and prognosis. In particular, the evidence accumulated to date suggests an important role of EVs in the initiation and progression of skin aging and various skin diseases, including psoriasis, systemic lupus erythematosus, vitiligo, and chronic wounds. This review highlights recent research that investigates the role of EVs and their potential as biomarkers and therapeutic agents for skin diseases and aging.

AI-Provided Instant Differential Diagnosis of Pemphigus Vulgaris and Bullous Pemphigoid: Qualitative Study (Preprint)

2020 ◽  
Author(s):  
Xiaoyu He ◽  
Juan Su ◽  
Guangyu Wang ◽  
Kang Zhang ◽  
Navarini Alexander ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Early Diagnosis ◽  
Image Classification ◽  
Bullous Pemphigoid ◽  
Skin Diseases ◽  
Pemphigus Vulgaris ◽  
Classification Model ◽  
Clinical Image ◽  
Clinical Images ◽  
Multimodal Classification

BACKGROUND Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are two rare but severe inflammatory dermatoses. Due to the regional lack of trained dermatologists, many patients with these two diseases are misdiagnosed and therefore incorrectly treated. An artificial intelligence diagnosis framework would be highly adaptable for the early diagnosis of these two diseases. OBJECTIVE Design and evaluate an artificial intelligence diagnosis framework for PV and BP. METHODS The work was conducted on a dermatological dataset consisting of 17,735 clinical images and 346 patient metadata of bullous dermatoses. A two-stage diagnosis framework was designed, where the first stage trained a clinical image classification model to classify bullous dermatoses from five common skin diseases and normal skin and the second stage developed a multimodal classification model of clinical images and patient metadata to further differentiate PV and BP. RESULTS The clinical image classification model and the multimodal classification model achieved an area under the receiver operating characteristic curve (AUROC) of 0.998 and 0.942, respectively. On the independent test set of 20 PV and 20 BP cases, our multimodal classification model (sensitivity: 0.85, specificity: 0.95) performed better than the average of 27 junior dermatologists (sensitivity: 0.68, specificity: 0.78) and comparable to the average of 69 senior dermatologists (sensitivity: 0.80, specificity: 0.87). CONCLUSIONS Our diagnosis framework based on clinical images and patient metadata achieved expert-level identification of PV and BP, and is potential to be an effective tool for dermatologists in remote areas in the early diagnosis of these two diseases.

scholarly journals An autophagy enhancer ameliorates diabetes of human IAPP-transgenic mice through clearance of amyloidogenic oligomer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jinyoung Kim ◽  
Kihyoun Park ◽  
Min Jung Kim ◽  
Hyejin Lim ◽  
Kook Hwan Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Therapeutic Modality ◽  
Protective Effects ◽  
Β Cells ◽  
Β Cell ◽  
Islet Amyloid ◽  
Amyloid Accumulation ◽  
Human Diabetes

AbstractWe have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and β-cell function of hIAPP+ mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.

scholarly journals Favorable Effects of GLP-1 Receptor Agonist against Pancreatic β-Cell Glucose Toxicity and the Development of Arteriosclerosis: “The Earlier, the Better” in Therapy with Incretin-Based Medicine

2021 ◽  
Vol 22 (15) ◽  
pp. 7917
Author(s):  
Hideaki Kaneto ◽  
Tomohiko Kimura ◽  
Masashi Shimoda ◽  
Atsushi Obata ◽  
Junpei Sanada ◽  
...  
Keyword(s):  
Large Scale ◽  
Cell Function ◽  
Apoptotic Cell ◽  
Early Stage ◽  
Insulin Biosynthesis ◽  
Protective Effects ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Toxicity

Fundamental pancreatic β-cell function is to produce and secrete insulin in response to blood glucose levels. However, when β-cells are chronically exposed to hyperglycemia in type 2 diabetes mellitus (T2DM), insulin biosynthesis and secretion are decreased together with reduced expression of insulin transcription factors. Glucagon-like peptide-1 (GLP-1) plays a crucial role in pancreatic β-cells; GLP-1 binds to the GLP-1 receptor (GLP-1R) in the β-cell membrane and thereby enhances insulin secretion, suppresses apoptotic cell death and increase proliferation of β-cells. However, GLP-1R expression in β-cells is reduced under diabetic conditions and thus the GLP-1R activator (GLP-1RA) shows more favorable effects on β-cells at an early stage of T2DM compared to an advanced stage. On the other hand, it has been drawing much attention to the idea that GLP-1 signaling is important in arterial cells; GLP-1 increases nitric oxide, which leads to facilitation of vascular relaxation and suppression of arteriosclerosis. However, GLP-1R expression in arterial cells is also reduced under diabetic conditions and thus GLP-1RA shows more protective effects on arteriosclerosis at an early stage of T2DM. Furthermore, it has been reported recently that administration of GLP-1RA leads to the reduction of cardiovascular events in various large-scale clinical trials. Therefore, we think that it would be better to start GLP-1RA at an early stage of T2DM for the prevention of arteriosclerosis and protection of β-cells against glucose toxicity in routine medical care.

Beta Cell Function is Disrupted in Patients with Systemic Lupus Erythematosus

Rheumatology ◽  
2020 ◽  
Author(s):  
Alicia García-Dorta ◽  
Juan Carlos Quevedo-Abeledo ◽  
Íñigo Rua-Figueroa ◽  
Antonia M de Vera-González ◽  
Alejandra González-Delgado ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Beta Cell ◽  
Lupus Erythematosus ◽  
Cell Function ◽  
Multivariable Analysis ◽  
Serum Levels ◽  
Cell Secretion ◽  
Systemic Lupus ◽  
Proinsulin Processing ◽  
Beta Cell Secretion

Abstract Introduction To investigate how markers of beta cell secretion (proinsulin-processing metabolites) are expressed in systemic lupus erythematosus (SLE) patients and their potential relation to features associated with the disease such as activity or damage. Methods 144 SLE patients and 69 nondiabetic sex- and age-matched controls were assessed. Beta-cell secretion molecules, as measured by insulin, split and intact proinsulins, and C-peptide levels were analyzed in both groups. Multiple regression analysis was performed to compare proinsulin propeptides between groups and to explore the interrelations with SLE features. Analyses were adjusted for glucocorticoid intake and for insulin resistance classic risk factors. Results Fully multivariable analysis demonstrated that regardless of glucocorticoid use, SLE patients exhibited higher levels of split proinsulin. Likewise, the split proinsulin-to-insulin ratio was upregulated in patients with SLE undergoing glucocorticoid therapy (beta coef. 0.19 [95%CI 0.07–0.30], p= 0.002) or not (beta coef. 0.09 [95%CI 0.01–0.17), p= 0.025). Similar results were found for the intact proinsulin-to-insulin ratio, although differences were only statistically significant for patients taking glucocorticoids (beta coef. 0.08 [95%CI 0.03–0.12], p= 0.001). SLE damage score was associated with higher serum levels of intact (beta coef. 0.51 [95%CI 0.17–0.86] pmol/l, p= 0.004) and split proinsulins (beta coef. 1.65 [95%CI 0.24–3.06] pmol/l, p= 0.022) after multivariable analysis, including disease duration and prednisone use. Conclusion Among patients with SLE, proinsulin-processing metabolites, a marker of beta-cell disruption, are upregulated compared with matched controls. This disproportionate hyperproinsulinemia can be explained by the damage produced by the disease and occurs independently of prednisone use.

scholarly journals Prostaglandin E2 Signaling Mediates Oenocytoid Immune Cell Function and Lysis, Limiting Bacteria and Plasmodium Oocyst Survival in Anopheles gambiae

2021 ◽  
Vol 12 ◽  
Author(s):  
Hyeogsun Kwon ◽  
David R. Hall ◽  
Ryan C. Smith
Keyword(s):  
Immune Responses ◽  
Prostaglandin E2 ◽  
Anopheles Gambiae ◽  
Cell Function ◽  
Immune Cell ◽  
Protective Effects ◽  
Immune Cell Function ◽  
Humoral Immune ◽  
High Concentrations ◽  
Prostaglandin E2 Receptor

Lipid-derived signaling molecules known as eicosanoids have integral roles in mediating immune and inflammatory processes across metazoans. This includes the function of prostaglandins and their cognate G protein-coupled receptors (GPCRs) to employ their immunological actions. In insects, prostaglandins have been implicated in the regulation of both cellular and humoral immune responses, yet in arthropods of medical importance, studies have been limited. Here, we describe a prostaglandin E2 receptor (AgPGE2R) in the mosquito Anopheles gambiae and demonstrate that its expression is most abundant in oenocytoid immune cell populations. Through the administration of prostaglandin E2 (PGE2) and AgPGE2R-silencing, we demonstrate that prostaglandin E2 signaling regulates a subset of prophenoloxidases (PPOs) and antimicrobial peptides (AMPs) that are strongly expressed in populations of oenocytoids. We demonstrate that PGE2 signaling via the AgPGE2R significantly limits both bacterial replication and Plasmodium oocyst survival. Additional experiments establish that PGE2 treatment increases phenoloxidase (PO) activity through the increased expression of PPO1 and PPO3, genes essential to anti-Plasmodium immune responses that promote oocyst killing. We also provide evidence that the mechanisms of PGE2 signaling are concentration-dependent, where high concentrations of PGE2 promote oenocytoid lysis, negating the protective effects of lower concentrations of PGE2 on anti-Plasmodium immunity. Taken together, our results provide new insights into the role of PGE2 signaling on immune cell function and its contributions to mosquito innate immunity that promote pathogen killing.

scholarly journals Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the unfolded protein response (UPR) in models of neurodegeneration

2020 ◽  
Author(s):  
René L. Vidal ◽  
Denisse Sepulveda ◽  
Paulina Troncoso-Escudero ◽  
Paula Garcia-Huerta ◽  
Constanza Gonzalez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Unfolded Protein Response ◽  
Target Genes ◽  
Cell Function ◽  
Alpha Synuclein ◽  
Protective Effects ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractAlteration to endoplasmic reticulum (ER) proteostasis is observed on a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteostasis and cell function. The UPR is initiated by specialized stress sensors that engage gene expression programs through the concerted action of the transcription factors ATF4, ATF6f, and XBP1s. Although UPR signaling is generally studied as unique linear signaling branches, correlative evidence suggests that ATF6f and XBP1s may physically interact to regulate a subset of UPR-target genes. Here, we designed an ATF6f-XBP1s fusion protein termed UPRplus that behaves as a heterodimer in terms of its selective transcriptional activity. Cell-based studies demonstrated that UPRplus has stronger an effect in reducing the abnormal aggregation of mutant huntingtin and alpha-synuclein when compared to XBP1s or ATF6 alone. We developed a gene transfer approach to deliver UPRplus into the brain using adeno-associated viruses (AAVs) and demonstrated potent neuroprotection in vivo in preclinical models of Parkinson’s and Huntington’s disease. These results support the concept where directing UPR-mediated gene expression toward specific adaptive programs may serve as a possible strategy to optimize the beneficial effects of the pathway in different disease conditions.

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