Search results for: skin fibrosis
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1122

Search results for: skin fibrosis

1122 Repositioning Sodium Valproate for Amelioration of Bleomycin-induced Scleroderma: The Role of Oxidative Stress, Transforming Growth Factor Beta-1, and the Mammalian Target of Rapamycin

Authors: Ahmed M. Kabel, Maaly A. Abd Elmaaboud

Abstract:

Scleroderma is one of the connective tissue disorders characterized by skin and systemic fibrosis. Its pathogenesis involves multiple interrelated processes of autoimmunity, vasculopathy, inflammation, and oxidative stress. This study was a trial to explore the possible ameliorative effects of sodium valproate on an experimental model of skin fibrosis induced by bleomycin. Forty male BALB/c mice were divided into four equal groups as follows: control group; bleomycin group; bleomycin + sodium valproate group, and sodium valproate group. Mice were assessed for their body weight every four days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 15, and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Also, the skin tissues were immunostained with alpha smooth muscle actin (α-SMA). Administration of sodium valproate to bleomycin-treated mice resulted in the restoration of the body weight with a significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression, and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone. In conclusion, sodium valproate has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for the management of scleroderma.

Keywords: scleroderma, bleomycin, sodium valproate, skin fibrosis

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1121 The Effect of Acute Rejection and Delayed Graft Function on Renal Transplant Fibrosis in Live Donor Renal Transplantation

Authors: Wisam Ismail, Sarah Hosgood, Michael Nicholson

Abstract:

The research hypothesis is that early post-transplant allograft fibrosis will be linked to donor factors and that acute rejection and/or delayed graft function in the recipient will be independent risk factors for the development of fibrosis. This research hypothesis is to explore whether acute rejection/delay graft function has an effect on the renal transplant fibrosis within the first year post live donor kidney transplant between 1998 and 2009. Methods: The study has been designed to identify five time points of the renal transplant biopsies [0 (pre-transplant), 1 month, 3 months, 6 months and 12 months] for 300 live donor renal transplant patients over 12 years period between March 1997 – August 2009. Paraffin fixed slides were collected from Leicester General Hospital and Leicester Royal Infirmary. These were routinely sectioned at a thickness of 4 Micro millimetres for standardization. Conclusions: Fibrosis at 1 month after the transplant was found significantly associated with baseline fibrosis (p<0.001) and HTN in the transplant recipient (p<0.001). Dialysis after the transplant showed a weak association with fibrosis at 1 month (p=0.07). The negative coefficient for HTN (-0.05) suggests a reduction in fibrosis in the absence of HTN. Fibrosis at 1 month was significantly associated with fibrosis at baseline (p 0.01 and 95%CI 0.11 to 0.67). Fibrosis at 3, 6 or 12 months was not found to be associated with fibrosis at baseline (p=0.70. 0.65 and 0.50 respectively). The amount of fibrosis at 1 month is significantly associated with graft survival (p=0.01 and 95%CI 0.02 to 0.14). Rejection and severity of rejection were not found to be associated with fibrosis at 1 month. The amount of fibrosis at 1 month was significantly associated with graft survival (p=0.02) after adjusting for baseline fibrosis (p=0.01). Both baseline fibrosis and graft survival were significant predictive factors. The amount of fibrosis at 1 month was not found to be significantly associated with rejection (p=0.64) after adjusting for baseline fibrosis (p=0.01). The amount of fibrosis at 1 month was not found to be significantly associated with rejection severity (p=0.29) after adjusting for baseline fibrosis (p=0.04). Fibrosis at baseline and HTN in the recipient were found to be predictive factors of fibrosis at 1 month. (p 0.02, p <0.001 respectively). Age of the donor, their relation to the patient, the pre-op Creatinine, artery, kidney weight and warm time were not found to be significantly associated with fibrosis at 1 month. In this complex model baseline fibrosis, HTN in the recipient and cold time were found to be predictive factors of fibrosis at 1 month (p=0.01,<0.001 and 0.03 respectively). Donor age was found to be a predictive factor of fibrosis at 6 months. The above analysis was repeated for 3, 6 and 12 months. No associations were detected between fibrosis and any of the explanatory variables with the exception of the donor age which was found to be a predictive factor of fibrosis at 6 months.

Keywords: fibrosis, transplant, renal, rejection

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1120 Prospective Validation of the FibroTest Score in Assessing Liver Fibrosis in Hepatitis C Infection with Genotype 4

Authors: G. Shiha, S. Seif, W. Samir, K. Zalata

Abstract:

Prospective Validation of the FibroTest Score in assessing Liver Fibrosis in Hepatitis C Infection with Genotype 4 FibroTest (FT) is non-invasive score of liver fibrosis that combines the quantitative results of 5 serum biochemical markers (alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, gamma glutamyl transpeptidase (GGT) and bilirubin) and adjusted with the patient's age and sex in a patented algorithm to generate a measure of fibrosis. FT has been validated in patients with chronic hepatitis C (CHC) (Halfon et al., Gastroenterol. Clin Biol.( 2008), 32 6suppl 1, 22-39). The validation of fibro test ( FT) in genotype IV is not well studied. Our aim was to evaluate the performance of FibroTest in an independent prospective cohort of hepatitis C patients with genotype 4. Subject was 122 patients with CHC. All liver biopsies were scored using METAVIR system. Our fibrosis score(FT) were measured, and the performance of the cut-off score were done using ROC curve. Among patients with advanced fibrosis, the FT was identically matched with the liver biopsy in 18.6%, overestimated the stage of fibrosis in 44.2% and underestimated the stage of fibrosis in 37.7% of cases. Also in patients with no/mild fibrosis, identical matching was detected in 39.2% of cases with overestimation in 48.1% and underestimation in 12.7%. So, the overall results of the test were identical matching, overestimation and underestimation in 32%, 46.7% and 21.3% respectively. Using ROC curve it was found that (FT) at the cut-off point of 0.555 could discriminate early from advanced stages of fibrosis with an area under ROC curve (AUC) of 0.72, sensitivity of 65%, specificity of 69%, PPV of 68%, NPV of 66% and accuracy of 67%. As FibroTest Score overestimates the stage of advanced fibrosis, it should not be considered as a reliable surrogate for liver biopsy in hepatitis C infection with genotype 4.

Keywords: fibrotest, chronic Hepatitis C, genotype 4, liver biopsy

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1119 Encoded Nanospheres for the Fast Ratiometric Detection of Cystic Fibrosis

Authors: Iván Castelló, Georgiana Stoica, Emilio Palomares, Fernando Bravo

Abstract:

We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of trypsin in humans. The system proved to be a faster (minutes) method, with two times higher sensitivity than the state-of-the-art biomarkers based sensors for cystic fibrosis (CF), allowing the quantification of trypsin concentrations in a wide range (0-350 mg/L). Furthermore, as trypsin is directly related to the development of cystic fibrosis, different human genotypes, i.e. healthy homozygotic (> 80 mg/L), CF homozygotic (< 50 mg/L), and heterozygotic (> 50 mg/L), respectively, can be determined using our 2nanoSi nanospheres.

Keywords: cystic fibrosis, trypsin, quantum dots, biomarker, homozygote, heterozygote

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1118 Comparison between Transient Elastography (FibroScan) and Liver Biopsy for Diagnosis of Hepatic Fibrosis in Chronic Hepatitis C Genotype 4

Authors: Gamal Shiha, Seham Seif, Shahera Etreby, Khaled Zalata, Waleed Samir

Abstract:

Background: Transient Elastography (TE; FibroScan®) is a non-invasive technique to assess liver fibrosis. Aim: To compare TE and liver biopsy in hepatitis C virus (HCV) patients, genotype IV and evaluate the effect of steatosis and schistosomiasis on FibroScan. Methods: The fibrosis stage (METAVIR Score) TE, was assessed in 519 patients. The diagnostic performance of FibroScan is assessed by calculating the area under the receiver operating characteristic curves (AUROCs). Results: The cut-off value of ≥ F2 was 8.55 kPa, ≥ F3 was 10.2 kPa and cirrhosis = F4 was 16.3 kPa. The positive predictive value and negative predictive value were 70.1% and 81.7% for the diagnosis of ≥ F2, 62.6% and 96.22% for F ≥ 3, and 27.7% and 100% for F4. No significant difference between schistosomiasis, steatosis degree and FibroScan measurements. Conclusion: Fibroscan could accurately predict liver fibrosis.

Keywords: chronic hepatitis C, FibroScan, liver biopsy, liver fibrosis

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1117 Improved Skin Detection Using Colour Space and Texture

Authors: Medjram Sofiane, Babahenini Mohamed Chaouki, Mohamed Benali Yamina

Abstract:

Skin detection is an important task for computer vision systems. A good method for skin detection means a good and successful result of the system. The colour is a good descriptor that allows us to detect skin colour in the images, but because of lightings effects and objects that have a similar colour skin, skin detection becomes difficult. In this paper, we proposed a method using the YCbCr colour space for skin detection and lighting effects elimination, then we use the information of texture to eliminate the false regions detected by the YCbCr colour skin model.

Keywords: skin detection, YCbCr, GLCM, texture, human skin

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1116 Analysis of Tactile Perception of Textiles by Fingertip Skin Model

Authors: Izabela L. Ciesielska-Wrόbel

Abstract:

This paper presents finite element models of the fingertip skin which have been created to simulate the contact of textile objects with the skin to gain a better understanding of the perception of textiles through the skin, so-called Hand of Textiles (HoT). Many objective and subjective techniques have been developed to analyze HoT, however none of them provide exact overall information concerning the sensation of textiles through the skin. As the human skin is a complex heterogeneous hyperelastic body composed of many particles, some simplifications had to be made at the stage of building the models. The same concerns models of woven structures, however their utilitarian value was maintained. The models reflect only friction between skin and woven textiles, deformation of the skin and fabrics when “touching” textiles and heat transfer from the surface of the skin into direction of textiles.

Keywords: fingertip skin models, finite element models, modelling of textiles, sensation of textiles through the skin

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1115 Therapeutic Evaluation of Bacopa Monnieri Extract on Liver Fibrosis in Rats

Authors: Yu Wen Wang, Shyh Ming Kuo, Hsia Ying Cheng, Yu Chiuan Wu

Abstract:

Liver fibrosis is caused by the activation of hepatic stellate cells in the liver to secrete excessive and deposition of extracellular matrix. In recent years, many treatment strategies have been developed to reduce the activation of hepatic stellate cells and therefore to increase the decomposition of extracellular matrix. Bacopa monnieri, an herbaceous plant of the scrophulariaceae, containing saponins and glycosides, which with antioxidant, anti-inflammation, pain relief and free radical scavenging characteristics. This study was to evaluate the inhibition of hepatic stellate cell activity by Bacopa monnieri extract and its therapeutic potential in treating thioacetamide-induced liver fibrosis in rats. The results showed that the IC50 of Bacopa monnieri extract was 0.39 mg/mL. Bacopa monnieri extract could effectively reduce H2O2-induced hepatic stellate cells inflammation. In the TAA-induced liver fibrosis animal studies, albumin secretion recovered to normal level after treated with Bacopa monnieri extract for 2-w, and fibrosis related proteins, α-SMA and TGF-1levels decreased indicating the extract exerted therapeutic effect on the liver fibrosis. However, inflammatory factors TNF- obviously decreased after 4-w treatment. In summary, we could successfully extract the main component-Bacopaside I from the plant and acquired a potential therapy using this component in treating TAA-induced liver fibrosis in rat.

Keywords: anti-inflammatory, Bacopa monnieri, fibrosis, hepatic stellate cells, water extract

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1114 Biopsy or Biomarkers: Which Is the Sample of Choice in Assessment of Liver Fibrosis?

Authors: S. H. Atef, N. H. Mahmoud, S. Abdrahman, A. Fattoh

Abstract:

Background: The aim of the study is to assess the diagnostic value of fibrotest and hyaluronic acid in discriminate between insignificant and significant fibrosis. Also, to find out if these parameters could replace liver biopsy which is currently used for selection of chronic hepatitis C patients eligible for antiviral therapy. Study design: This study was conducted on 52 patients with HCV RNA detected by polymerase chain reaction (PCR) who had undergone liver biopsy and attending the internal medicine clinic at Ain Shams University Hospital. Liver fibrosis was evaluated according to the METAVIR scoring system on a scale of F0 to F4. Biochemical markers assessed were: alpha-2 macroglobulin (α2-MG), apolipoprotein A1 (Apo-A1), haptoglobin, gamma-glutamyl transferase (GGT), total bilirubin (TB) and hyaluronic acid (HA). The fibrotest score was computed after adjusting for age and gender. Predictive values and ROC curves were used to assess the accuracy of fibrotest and HA results. Results: For fibrotest, the observed area under curve for the discrimination between minimal or no fibrosis (F0-F1) and significant fibrosis (F2-F4) was 0.6736 for cutoff value 0.19 with sensitivity of 84.2% and specificity of 85.7%. For HA, the sensitivity was 89.5% and specificity was 85.7% and area under curve was 0.540 at the best cutoff value 71 mg/dL. Multi-use of both parameters, HA at 71 mg/dL with fibrotest score at 0.22 give a sensitivity 89.5%, specificity 100 and efficacy 92.3% (AUC 0.895). Conclusion: The use of both fibrotest score and HA could be as alternative to biopsy in most patients with chronic hepaitis C putting in consideration some limitations of the proposed markers in evaluating liver fibrosis.

Keywords: fibrotest, liver fibrosis, HCV RNA, biochemical markers

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1113 Penetration Depth Study of Linear Siloxanes through Human Skin

Authors: K. Szymkowska, K. Mojsiewicz- Pieńkowska

Abstract:

Siloxanes are a common ingredients in medicinal products used on the skin, as well as cosmetics. It is widely believed that the silicones are not capable of overcoming the skin barrier. The aim of the study was to verify the possibility of penetration and permeation of linear siloxanes through human skin and determine depth penetration limit of these compounds. Based on the results it was found that human skin is not a barrier for linear siloxanes. PDMS 50 cSt was not identified in the dermis suggests that this molecular size of silicones (3780Da) is safe when it is used in the skin formulations.

Keywords: linear siloxanes, methyl siloxanes, skin penetration, skin permeation

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1112 Sulforaphane Attenuates Fibrosis of Dystrophic Muscle in Mdx Mice via Nrf2-Mediated Inhibition of TGF-β/Smad Signaling

Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Yongyong Xi, Liang Wang, Dejia Li

Abstract:

Backgrounds: A few lines of evidence show that Sulforaphane (SFN) has anti-fibrosis effect in liver tissue via Nrf2-mediated inhibition of TGF-β/Smad signaling. However, its effects on muscular dystrophic fibrosis remain unknown. This work was undertaken to evaluate the effects of SFN on fibrosis in dystrophic muscle. Methods: 3-month-old male mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 3 months. Gastrocnemius, tibial anterior and triceps brachii muscles were collected for related analysis. Fibrosis in skeletal muscles was analyzed by Sirius red staining. Histology and morphology of skeletal muscles were investigated by H&E staining. Moreover, the expressions of Nrf2, NQO1, HO-1, and TGF-β/Smad signaling pathway were detected by western blot, qRT-PCR, immunohistochemistry and immunofluorescence assays. Results: Our results demonstrated that SFN treatment significantly decreased and improved morphological features in mdx muscles. Moreover, SFN increased the expression of muscle phase II enzymes NQO1 and HO-1 and significantly decreased the expression of TGF-β1,p-smad2, p-smad3, α-SMA, fibronectin, collagen I, PAI-1, and TIMP-1 in Nrf2 dependent manner. Additionally, SFN significantly decreased the expression of CD45 and TNF-α. Conclusions: Collectively, these results show that SFN can ameliorate muscle fibrosis in mdx mice by Nrf2-induced inhibition of TGF-β/Smad signaling pathway, which indicate Nrf2 may be useful for the treatment of muscular dystrophy.

Keywords: sulforaphane, Nrf2, TGF-β/smad signaling, duchenne muscular dystrophy, fibrosis

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1111 Effect of Nicorandil in Bile Duct Ligation-Induced Liver Fibrosis in Rats: Role of Hepatic Stellate Cells

Authors: Y. S. Mohamed, L. A. Ahmed, H. A. Salem, A. M. Agha

Abstract:

Liver Fibrosis is one of the most serious conditions that affect the Egyptian society. In the present study, the effect of nicorandil was investigated in experimentally-induced liver fibrosis by bile duct ligation in rats. Nicorandil (3mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed a significant improvement in liver function tests (ALT and ALP) as well as a significant decrease in oxidative stress biomarkers (TBARS and GSH), area of fibrosis and activity of hepatic stellate cells as indicated by decreased expression of alpha smooth muscle actin.Moreover, nicorandil treatment decreased HSCs proliferation due to its inhibitory effects on protein kinase C(PKC) and Platelet derived growth factor (PDGF) . Oral administration of either glibenclamide (10 mg/kg/day)(a KATP channel blocker) or L-NAME (30 mg/kg/day) (an inhibitor of nitric oxide synthase) blocked the protective effects of nicorandil. However, nicorandil and L-NAME treated group showed more or less results similar to that of untreated bile duct ligated group. In conclusion, nicorandil was effective against the development of bile duct ligated-induced liver fibrosis in rats where activation of the NO pathway plays an important role in the protective effect nicorandil.

Keywords: hepatic stellate cells, nicorandil, nitric oxide donor, liver fibrosis

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1110 Skin Care through Ayurveda

Authors: K. L. Virupaksha Gupta

Abstract:

Ayurveda offers a holistic outlook regarding skin care. Most Initial step in Ayurveda is to identify the skin type and care accordingly which is highly personalized. Though dermatologically there are various skin type classifications such Baumann skin types (based on 4 parameters i) Oily Vs Dry ii) Sensitive Vs Resistant iii) Pigmented Vs Non-Pigmented iv) Wrinkled Vs Tight (Unwrinkled) etc but Skin typing in Ayurveda is mainly determined by the prakriti (constitution) of the individual as well as the status of Doshas (Humors) which are basically of 3 types – i.e Vata Pitta and Kapha,. Difference between them is mainly attributed to the qualities of each dosha (humor). All the above said skin types can be incorporated under these three types. The skin care modalities in each of the constitution vary greatly. Skin of an individual of Vata constitution would be lustreless, having rough texture and cracks due to dryness and thus should be given warm and unctuous therapies and oil massage for lubrication and natural moisturizers for hydration. Skin of an individual of Pitta constitution would look more vascular (pinkish), delicate and sensitive with a fair complexion, unctuous and tendency for wrinkles and greying of hair at an early age and hence should be given cooling and nurturing therapies and should avoid tanning treatments. Skin of an individual of kapha constitution will have oily skin, they are delicate and look beautiful and radiant and hence these individuals would require therapies to mainly combat oily skin. Hence, the skin typing and skin care in Ayurveda is highly rational and scientific.

Keywords: Ayurveda, dermatology, Dosha, skin types

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1109 Green Tea Extract: Its Potential Protective Effect on Bleomycin Induced Lung Injuries in Rats

Authors: Azza EL-Medany, Jamila EL-Medany

Abstract:

Lung fibrosis is a common side effect of the chemotherapeutic agent, bleomycin. Current evidence suggests that reactive oxygen species may play a key role in the development of lung fibrosis. The present work studied the effect of green tea extract on bleomycin–induced lung fibrosis in rats. Animals were divided into three groups: (1) Saline control group; (2) bleomycin group in which rats were injected with bleomycin (15mg/kg,i.p.) three times a week for four weeks; (3) bleomycin and green tea group in which green tea extract was given to rats (100mg/kg/day, p.o) a week prior to bleomycin and daily during bleomycin injections for 4 weeks until the end of the experiment. Bleomycin–induced pulmonary injury and lung fibrosis that was indicated by increased lung hydroxyproline content, elevated nitric oxide synthase, myeoloperoxidase (MPO), platelet activating factor (PAF), tumor necrosis factor α (TNF_α), transforming growth factor 1β (TGF1β) and angiotensin converting enzyme (ACE) activity in lung tissues. On the other hand, bleomycin induced a reduction in reduced glutathione concentration (GSH). Moreover, bleomycin resulted in a severe histological changes in lung tissues revealed as lymphocytes and neutrophils infiltration, increased collagen deposition and fibrosis. Co-administration of bleomycin and green tea extract reduced bleomycin–induced lung injury as evaluated by the significant reduction in hydroxyproline content, nitric oxide synthase activity, levels of MPO, PAF, TNF-α, and ACE in lung tissues. Furthermore, green tea extract ameliorated bleomycin– induced reduction in GSH concentration. Finally, histological evidence supported the ability of green tea extract to attenuate bleomycin–induced lung fibrosis and consolidation. Thus, the finding of the present study provides that green tea may serve as a novel target for potential therapeutic treatment of lung fibrosis.

Keywords: bleomycin, lung fibrosis, green tea, oxygen species

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1108 Curcumin Attenuates Angiogenesis in Liver Fibrosis and Inhibits Angiogenic Properties of Hepatic Stellate Cells

Authors: Feng Zhang, Li Chen, Desong Kong, Xiaoping Zhang, Xiaojing Zhu, Yin Lu, Shizhong Zheng

Abstract:

Sinusoidal pathological angiogenesis is a novel therapeutic target for liver fibrosis. We demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells (LSECs) were not impaired by curcumin. Further investigations showed that curcumin inhibited VEGF expression in hepatic stellate cells (HSCs) by disrupting PDGF-βR/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin via blocking PDGF-βR/FAK/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of PPARγ was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPARγ activation-dependent mechanism. PPARγ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.

Keywords: angiogenesis, hepatic stellate cell, curcumin, peroxisome proliferator-activated receptor-γ

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1107 Towards Integrating Statistical Color Features for Human Skin Detection

Authors: Mohd Zamri Osman, Mohd Aizaini Maarof, Mohd Foad Rohani

Abstract:

Human skin detection recognized as the primary step in most of the applications such as face detection, illicit image filtering, hand recognition and video surveillance. The performance of any skin detection applications greatly relies on the two components: feature extraction and classification method. Skin color is the most vital information used for skin detection purpose. However, color feature alone sometimes could not handle images with having same color distribution with skin color. A color feature of pixel-based does not eliminate the skin-like color due to the intensity of skin and skin-like color fall under the same distribution. Hence, the statistical color analysis will be exploited such mean and standard deviation as an additional feature to increase the reliability of skin detector. In this paper, we studied the effectiveness of statistical color feature for human skin detection. Furthermore, the paper analyzed the integrated color and texture using eight classifiers with three color spaces of RGB, YCbCr, and HSV. The experimental results show that the integrating statistical feature using Random Forest classifier achieved a significant performance with an F1-score 0.969.

Keywords: color space, neural network, random forest, skin detection, statistical feature

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1106 Regression of Fibrosis by Apigenin in Thioacetamide-Induced Liver Fibrosis Rat Model through Suppression of HIF-1/FAK Pathway

Authors: Hany M. Fayed, Rehab F. Abdel-Rahman, Alyaa F. Hessin, Hanan A. Ogaly, Gihan F. Asaad, Abeer A. A. Salama, Sahar Abdelrahman, Mahmoud S. Arbid, Marwan Abd Elbaset Mohamed

Abstract:

Liver fibrosis is a serious global health problem that occurs as a result of a variety of chronic liver disorders. Apigenin, a flavonoid found in many plants, has several pharmacological properties. The aim of this study was to evaluate the antifibrotic efficacy of apigenin (APG) against experimentally induced hepatic fibrosis in rats via using thioacetamide (TAA) and to explore the possible underlying mechanisms. TAA (100 mg/kg, i.p.) was given three times each week for two weeks to induce liver fibrosis. After TAA injections, APG was given orally (5 and 10 mg/kg) daily for two weeks. Biochemical, molecular, histological and immunohistochemical analyses were performed on blood and liver tissue samples. The functioning of the liver, oxidative stress, inflammation, and liver fibrosis indicators were all evaluated. The findings showed that TAA markedly increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of malondialdehyde (MDA), focal adhesion kinase (FAK), hypoxia-inducible factor-1 (HIF-1), nuclear factor-κB (NF-κB), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) with a reduction in albumin, total protein, A/G ratio, GSH content and interleukin-10 (IL-10). Moreover, TAA elevated the content of collagen I, α -smooth muscle actin (α-SMA), and hydroxyproline in the liver. The treatment with APG in a dose-dependent manner has obviously prevented these alterations and amended the harmful effects induced by TAA. The histopathological and immunohistochemical observations supported this biochemical evidence. The higher dose of APG produced the most significant antifibrotic effect. As a result of these data, APG appears to be a promising antifibrotic drug and could be used as a new herbal medication or dietary supplement in the future for the treatment of liver fibrosis. This effect might be related to the inhibition of the HIF-1/FAK signaling pathway.

Keywords: apigenin, FAK, HIF-1, liver fibrosis, rat, thioacetamide

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1105 Analysis of the Lung Microbiome in Cystic Fibrosis Patients Using 16S Sequencing

Authors: Manasvi Pinnaka, Brianna Chrisman

Abstract:

Cystic fibrosis patients often develop lung infections that range anywhere in severity from mild to life-threatening due to the presence of thick and sticky mucus that fills their airways. Since many of these infections are chronic, they not only affect a patient’s ability to breathe but also increase the chances of mortality by respiratory failure. With a publicly available dataset of DNA sequences from bacterial species in the lung microbiome of cystic fibrosis patients, the correlations between different microbial species in the lung and the extent of deterioration of lung function were investigated. 16S sequencing technologies were used to determine the microbiome composition of the samples in the dataset. For the statistical analyses, referencing helped distinguish between taxonomies, and the proportions of certain taxa relative to another were determined. It was found that the Fusobacterium, Actinomyces, and Leptotrichia microbial types all had a positive correlation with the FEV1 score, indicating the potential displacement of these species by pathogens as the disease progresses. However, the dominant pathogens themselves, including Pseudomonas aeruginosa and Staphylococcus aureus, did not have statistically significant negative correlations with the FEV1 score as described by past literature. Examining the lung microbiology of cystic fibrosis patients can help with the prediction of the current condition of lung function, with the potential to guide doctors when designing personalized treatment plans for patients.

Keywords: bacterial infections, cystic fibrosis, lung microbiome, 16S sequencing

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1104 Fabrication of Optical Tissue Phantoms Simulating Human Skin and Their Application

Authors: Jihoon Park, Sungkon Yu, Byungjo Jung

Abstract:

Although various optical tissue phantoms (OTPs) simulating human skin have been actively studied, their completeness is unclear because skin tissue has the intricate optical property and complicated structure disturbing the optical simulation. In this study, we designed multilayer OTP mimicking skin structure, and fabricated OTP models simulating skin-blood vessel and skin pigmentation in the skin, which are useful in Biomedical optics filed. The OTPs were characterized with the optical property and the cross-sectional structure, and analyzed by using various optical tools such as a laser speckle imaging system, OCT and a digital microscope to show the practicality. The measured optical property was within 5% error, and the thickness of each layer was uniform within 10% error in micrometer scale.

Keywords: blood vessel, optical tissue phantom, optical property, skin tissue, pigmentation

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1103 Overview and Pathophysiology of Radiation-Induced Breast Changes as a Consequence of Radiotherapy Toxicity

Authors: Monika Rezacova

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Radiation-induced breast changes are a consequence of radiotherapy toxicity over the breast tissues either related to targeted breast cancer treatment or other thoracic malignancies (eg. lung cancer). This study has created an overview of different changes and their pathophysiology. The main conditions included were skin thickening, interstitial oedema, fat necrosis, dystrophic calcifications, skin retractions, glandular atrophy, breast fibrosis and radiation induced breast cancer. This study has performed focused literature search through multiple databases including pubmed, medline and embase. The study has reviewed English as well as non English publications. As a result of the literature the study provides comprehensive overview of radiation-induced breast changes and their pathophysiology with small focus on new development and prevention.

Keywords: radiotherapy toxicity, breast tissue changes, breast cancer treatment, radiation-induced breast changes

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1102 Classification of Red, Green and Blue Values from Face Images Using k-NN Classifier to Predict the Skin or Non-Skin

Authors: Kemal Polat

Abstract:

In this study, it has been estimated whether there is skin by using RBG values obtained from the camera and k-nearest neighbor (k-NN) classifier. The dataset used in this study has an unbalanced distribution and a linearly non-separable structure. This problem can also be called a big data problem. The Skin dataset was taken from UCI machine learning repository. As the classifier, we have used the k-NN method to handle this big data problem. For k value of k-NN classifier, we have used as 1. To train and test the k-NN classifier, 50-50% training-testing partition has been used. As the performance metrics, TP rate, FP Rate, Precision, recall, f-measure and AUC values have been used to evaluate the performance of k-NN classifier. These obtained results are as follows: 0.999, 0.001, 0.999, 0.999, 0.999, and 1,00. As can be seen from the obtained results, this proposed method could be used to predict whether the image is skin or not.

Keywords: k-NN classifier, skin or non-skin classification, RGB values, classification

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1101 MiR-200a/ZEB1 Pathway in Liver Fibrogenesis of Biliary Atresia

Authors: Hai-Ying Liu, Yi-Hao Chen, Shu-Yin Pang, Feng-Hua Wang, Xiao-Fang Peng, Li-Yuan Yang, Zheng-Rong Chen, Yi Chen, Bing Zhu

Abstract:

Objective: Biliary atresia (BA) is characterized by progressive liver fibrosis. Epithelial-mesenchymal transition (EMT) has been implicated as a key mechanism in the pathogenesis of organ fibrosis. MiR-200a has been shown to repress EMT. We aim to explore the role of miR-200a in the fibrogenesis of BA. Methods: We obtained the plasma samples and liver samples from patients with BA or controls to examine the role of miR-200a. Histological liver fibrosis was assessed using the Ishak fibrosis scores. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of miR-200a in plasma. We also evaluated the expression of miR-200a in liver tissues using tyramide signal amplification fluorescence in situ hybridization (TSA-FISH). The expression of EMT related proteins zinc finger E-box-binding homeobox 1 (ZEB1), E-cadherin and α-smooth muscle actin (α-SMA) in the liver sections were detected by immunohistochemical staining. Results: We found that the expression of miR-200a was both elevated in the plasma and liver tissues from BA patients compared with the controls. The hepatic expression of ZEB1 and α-SMA were markedly increased in the liver sections from BA patients compared to the controls, whereas E-cadherin was downregulated in the BA group. Simultaneously, we noted that the hepatic expression of miR-200a, E-cadherin and α-SMA were upregulated with the progression of liver fibrosis in the BA group, while ZEB1 was downregulated with the progression of liver fibrosis in BA patients. Conclusion: These findings suggest EMT has a critical effect on the fibrotic process of BA, and the interaction between miR-200a and ZEB1 may regulate EMT and eventually influence liver fibrogenesis of BA.

Keywords: biliary atresia, liver fibrosis, MicroRNA, epithelial-mesenchymal transition, zinc finger E-box-binding homeobox 1

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1100 The Impact of Lipids on Lung Fibrosis

Authors: G. Wojcik, J. Gindlhuber, A. Syarif, K. Hoetzenecker, P. Bohm, P. Vesely, V. Biasin, G. Kwapiszewska

Abstract:

Pulmonary fibrosis is a rare disease where uncontrolled wound healing processes damage the lung structure. Intensive changes within the extracellular matrix (ECM) and its interaction with fibroblasts have a major role in pulmonary fibrosis development. Among others, collagen is one of the main components of the ECM, and it is important for lung structure. In IPF, constant production of collagen by fibroblast, through TGFβ1-SMAD2/3 pathways, leads to an uncontrolled deposition of matrix and hence lung remodeling. Abnormal changes in lipid production, alterations in fatty acids (FAs) metabolism, enhanced oxidative stress, and lipid peroxidation in fibrotic lung and fibrotic fibroblasts have been reported; however, the interplay between the collagen and lipids is not yet established. One of the FAs influx regulators is Angiopoietin-like 4 (ANGPTL4), which inhibits lipoprotein lipase work, decreasing the availability of FAs. We hypothesized that altered lipid composition or availability could have the capability to influence the phenotype of different fibroblast populations in the lung and hence influence lung fibrosis. To prove our hypothesis, we aim to investigate lipids and their influence on human, animal, and in vitro levels. In the bleomycin model, treatment with the well-known metabolic drugs Rosiglitazone or Metformin significantly lower collagen production. Similar results were noticed in ANGPTL4 KO animals, where the KO of ANGPTL4 leads to an increase of FAs availability and lower collagen deposition after the bleomycin challenge. Currently, we study the treatment of different FAs on human lung para fibroblasts (hPF) isolated from donors. To understand the lipid composition, we are collecting human lung tissue from donors and pulmonary fibrosis patients for Liquid chromatography-mass spectrometry. In conclusion, our results suggest the lipid influence on collagen deposition during lung fibrosis, but further research needs to be conducted to understand the matter of this relationship.

Keywords: collagen, fibroblasts, lipidomics, lung, pulmonary fibrosis

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1099 Curcumin Reduces the Expression of Main Fibrogenic Genes and Phosphorylation of Smad3C Signaling Pathway in TGFB-Activated Human HSCs. A New Remedy for Liver Fibrosis

Authors: Elham Shakerian, Reza Afarin

Abstract:

The hepatic disease causes approximately 2 million deaths/year worldwide. Liver fibrosis is the last stage of numerous chronic liver diseases, and until now there is no definite cure or drug for it. Activation of hepatic stellate cells (HSCs) is the main reason for fibrosis. Transforming growth factor (TGF-β), as a main profibrogenic cytokine, if increased in these cells, leads to liver fibrosis through smad3 signaling pathways and increasing the expressions of Collagen type I and III, and actin-alpha smooth muscle (αSMA) genes. Curcumin (CUR) is a polyphenolic compound and an active ingredient derived from the rhizome of the turmeric plant that exerts effective antioxidant, anti-inflammatory, and antimicrobial activity. It has been shown that daily consumption of curcumin may have a protective effect on the liver against oxidative stress associated with alcohol consumption. In this study, we investigate the role of Curcumin in decreasing HSC activation and treating liver fibrosis. First, the human HSCs were treated with 2 ng/ml of (TGF-β) for 24 hours to become activated, then with Silibinin for 24 hours. Total RNAs were extracted, reversely transcribed into cDNA, Quantitative Real-time PCR, and western blot were performed. The mRNA expression levels of Collagen type I and III, αSMA genes, and the level of smad3 phosphorylation in TGF-β activated human HSCs treated with Curcumin were significantly reduced compared to human HSCs untreated with Curcumin. Curcumin is effective in reducing the expression of fibrogenic genes in the activated human HSCs treated with TGFB through downregulation of the TGF-β/smad3 signaling pathway. Therefore, Curcumin possesses significant antifibrotic properties in hepatic fibrosis

Keywords: hepatic fibrosis, human HSCs, curcumin, fibrogenic genes

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1098 The Effect of Skin to Skin Contact Immediately to Maternal Breastfeeding Self-Efficacy after Cesarean Section

Authors: D. Triana, I. N. Rachmawati, L. Sabri

Abstract:

Maternal breastfeeding self-efficacy is positively associated with increased duration of breastfeeding in different cultures and age groups. This study aims to determine the effect of skin-to-skin contact immediately after the cesarean section on maternal breastfeeding self-efficacy. The research design is Posttest quasi-experimental research design only with control groups involving 52 women with consecutive sampling in Langsa-Aceh. The data collected through breastfeeding Self-Efficacy Scale-Short Form. The results of Independent t-test showed a significant difference in the mean values of maternal breastfeeding self-efficacy in the intervention group and the control group (59.00 ± 6.54; 49.62 ± 7.78; p= 0.001). Skin to skin contact is proven to affect the maternal breastfeeding self-efficacy after cesarean section significantly.

Keywords: breastfeeding self-efficacy, cesarean section, skin to skin contact, immediately

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1097 Rebamipide Retards CCL4 Induced Hepatic Fibrosis: A Role of PGE2

Authors: Alaa E. El-sisi, Sherin Zakaria

Abstract:

Rebamipide is an antiulcer drug with unique properties such as anti-inflammatory action. It induces endogenous prostaglandin e2 (PGE2). PGE2 is considered as a potent physiological suppressor of liver fibrosis. Aim of study: This study investigated the effect of rebamipide on hepatic fibrosis. Material and Method: Hepatic fibrosis was induced by intraperitoneal injections (IP) injection of CCl4 (0.45 mL/kg) in corn oil 1:5 twice a week for 4 weeks. Rats were divided into four groups as follow: Group 1 treated with CCL4 only, group 2 and 3 treated with CCL4 and rebamipide 60 mg/kg/day (group2) or 100 mg/kg/day (group3), and the fourth group was considered as control group and treated with vehicles. ALT, AST, and Bilirubin were assayed in serum. Antioxidant markers such as malondialdhyde (MDA) and superoxide dismutase (SOD) and fibrotic markers such as hyaluronic acid (HA) and procollagen-III (procol-III) were evaluated in liver tissues. IL-10 as well as PGE2 were also assayed in liver tissues. Pathologic changes in the liver were detected by hematoxylin and eosin staining. Collagen precipitation in liver tissues was visualized using masson trichrom stain. Results: Rebamipide inhibit CCL4 induced increase in ALT and AST significantly (p < 0.05). Rebamipide exerted an antioxidant effect as it inhibits CCL4 induced increased MDA level and decreased SOD activity. Fibrotic markers assay revealed that repamipide (60 or 100 mg/kg/day) decreased the level of procol-III and HA compared to CCl4 (p < 0.05). Oral administration of Rebamipide was associated with a significant increase (p < 0.05) of PGE2 and IL-10. Rebamipide especially at the dose of (100 mg/kg/day) restores liver histology structure and abolish collagen precipitation in liver tissues. Conclusion: Rebamipide retards hepatic fibrosis induced by CCL4 may be through the induction of PGE2 level.

Keywords: fibrotic markers, hepatic fibrosis, PGE2, rebamipide

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1096 A Convolutional Deep Neural Network Approach for Skin Cancer Detection Using Skin Lesion Images

Authors: Firas Gerges, Frank Y. Shih

Abstract:

Malignant melanoma, known simply as melanoma, is a type of skin cancer that appears as a mole on the skin. It is critical to detect this cancer at an early stage because it can spread across the body and may lead to the patient's death. When detected early, melanoma is curable. In this paper, we propose a deep learning model (convolutional neural networks) in order to automatically classify skin lesion images as malignant or benign. Images underwent certain pre-processing steps to diminish the effect of the normal skin region on the model. The result of the proposed model showed a significant improvement over previous work, achieving an accuracy of 97%.

Keywords: deep learning, skin cancer, image processing, melanoma

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1095 Effects of Bone Marrow Derived Mesenchymal Stem Cells (MSC) in Acute Respiratory Distress Syndrome (ARDS) Lung Remodeling

Authors: Diana Islam, Juan Fang, Vito Fanelli, Bing Han, Julie Khang, Jianfeng Wu, Arthur S. Slutsky, Haibo Zhang

Abstract:

Introduction: MSC delivery in preclinical models of ARDS has demonstrated significant improvements in lung function and recovery from acute injury. However, the role of MSC delivery in ARDS associated pulmonary fibrosis is not well understood. Some animal studies using bleomycin, asbestos, and silica-induced pulmonary fibrosis show that MSC delivery can suppress fibrosis. While other animal studies using radiation induced pulmonary fibrosis, liver, and kidney fibrosis models show that MSC delivery can contribute to fibrosis. Hypothesis: The beneficial and deleterious effects of MSC in ARDS are modulated by the lung microenvironment at the time of MSC delivery. Methods: To induce ARDS a two-hit mouse model of Hydrochloric acid (HCl) aspiration (day 0) and mechanical ventilation (MV) (day 2) was used. HCl and injurious MV generated fibrosis within 14-28 days. 0.5x106 mouse MSCs were delivered (via both intratracheal and intravenous routes) either in the active inflammatory phase (day 2) or during the remodeling phase (day 14) of ARDS (mouse fibroblasts or PBS used as a control). Lung injury accessed using inflammation score and elastance measurement. Pulmonary fibrosis was accessed using histological score, tissue collagen level, and collagen expression. In addition alveolar epithelial (E) and mesenchymal (M) marker expression profile was also measured. All measurements were taken at day 2, 14, and 28. Results: MSC delivery 2 days after HCl exacerbated lung injury and fibrosis compared to HCl alone, while the day 14 delivery showed protective effects. However in the absence of HCl, MSC significantly reduced the injurious MV-induced fibrosis. HCl injury suppressed E markers and up-regulated M markers. MSC delivery 2 days after HCl further amplified M marker expression, indicating their role in myofibroblast proliferation/activation. While with 14-day delivery E marker up-regulation was observed indicating their role in epithelial restoration. Conclusions: Early MSC delivery can be protective of injurious MV. Late MSC delivery during repair phase may also aid in recovery. However, early MSC delivery during the exudative inflammatory phase of HCl-induced ARDS can result in pro-fibrotic profiles. It is critical to understand the interaction between MSC and the lung microenvironment before MSC-based therapies are utilized for ARDS.

Keywords: acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC), hydrochloric acid (HCl), mechanical ventilation (MV)

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1094 Quality Rabbit Skin Gelatin with Acetic Acid Extract

Authors: Wehandaka Pancapalaga

Abstract:

This study aimed to analyze the water content, yield, fat content, protein content, viscosity, gel strength, pH, melting and organoleptic rabbit skin gelatin with acetic acid extraction levels are different. The materials used in this study were Rex rabbit skin male. Treatments that P1 = the extraction of acetic acid 2% (v / v); P2 = the extraction of acetic acid 3% (v / v); P3 = the extraction of acetic acid 4 % (v / v). P5 = the extraction of acetic acid 5% (v / v). The results showed that the greater the concentration of acetic acid as the extraction of rabbit skin can reduce the water content and fat content of rabbit skin gelatin but increase the protein content, viscosity, pH, gel strength, yield and melting point rabbit skin gelatin. texture, color and smell of gelatin rabbits there were no differences with cow skin gelatin. The results showed that the quality of rabbit skin gelatin accordance Indonesian National Standard (SNI). Conclusion 5% acetic acid extraction produces the best quality gelatin.

Keywords: gelatin, skin rabbit, acetic acid extraction, quality

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1093 Electrospun Nanofibrous Scaffolds Modified with Collagen-I and Fibronectin with LX-2 Cells to Study Liver Fibrosis in vitro

Authors: Prativa Das, Lay Poh Tan

Abstract:

Three-dimensional microenvironment is a need to study the event cascades of liver fibrosis in vitro. Electrospun nanofibers modified with essential extracellular matrix proteins can closely mimic the random fibrous structure of native liver extracellular matrix (ECM). In this study, we fabricate a series of 3D electrospun scaffolds by wet electrospinning process modified with different ratios of collagen-I to fibronectin to achieve optimized distribution of these two ECM proteins on the fiber surface. A ratio of 3:1 of collagen-I to fibronectin was found to be optimum for surface modification of electrospun poly(lactic-co-glycolic acid) (PLGA) fibers by chemisorption process. In 3:1 collagen-I to fibronectin modified scaffolds the total protein content increased by ~2 fold compared to collagen-I modified and ~1.5 fold compared to 1:1/9:1 collagen-I to fibronectin modified scaffolds. We have cultured LX-2 cells on this scaffold over 14 days and found that LX-2 cells acquired more quiescent phenotype throughout the culture period and shown significantly lower expression of alpha smooth muscle actin and collagen-I. Thus, this system can be used as a model to study liver fibrosis by using different fibrogenic mediators in vitro.

Keywords: electrospinning, collagen-I and fibronectin, surface modification of fiber, LX-2 cells, liver fibrosis

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