Search results for: human skin and hair cells
Commenced in January 2007
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Edition: International
Paper Count: 11300

Search results for: human skin and hair cells

11180 Changes in Skin Microbiome Diversity According to the Age of Xian Women

Authors: Hanbyul Kim, Hye-Jin Kin, Taehun Park, Woo Jun Sul, Susun An

Abstract:

Skin is the largest organ of the human body and can provide the diverse habitat for various microorganisms. The ecology of the skin surface selects distinctive sets of microorganisms and is influenced by both endogenous intrinsic factors and exogenous environmental factors. The diversity of the bacterial community in the skin also depends on multiple host factors: gender, age, health status, location. Among them, age-related changes in skin structure and function are attributable to combinations of endogenous intrinsic factors and exogenous environmental factors. Skin aging is characterized by a decrease in sweat, sebum and the immune functions thus resulting in significant alterations in skin surface physiology including pH, lipid composition, and sebum secretion. The present study gives a comprehensive clue on the variation of skin microbiota and the correlations between ages by analyzing and comparing the metagenome of skin microbiome using Next Generation Sequencing method. Skin bacterial diversity and composition were characterized and compared between two different age groups: younger (20 – 30y) and older (60 - 70y) Xian, Chinese women. A total of 73 healthy women meet two conditions: (I) living in Xian, China; (II) maintaining healthy skin status during the period of this study. Based on Ribosomal Database Project (RDP) database, skin samples of 73 participants were enclosed with ten most abundant genera: Chryseobacterium, Propionibacterium, Enhydrobacter, Staphylococcus and so on. Although these genera are the most predominant genus overall, each genus showed different proportion in each group. The most dominant genus, Chryseobacterium was more present relatively in Young group than in an old group. Similarly, Propionibacterium and Enhydrobacter occupied a higher proportion of skin bacterial composition of the young group. Staphylococcus, in contrast, inhabited more in the old group. The beta diversity that represents the ratio between regional and local species diversity showed significantly different between two age groups. Likewise, The Principal Coordinate Analysis (PCoA) values representing each phylogenetic distance in the two-dimensional framework using the OTU (Operational taxonomic unit) values of the samples also showed differences between the two groups. Thus, our data suggested that the composition and diversification of skin microbiomes in adult women were largely affected by chronological and physiological skin aging.

Keywords: next generation sequencing, age, Xian, skin microbiome

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11179 Study the Effect of Dermal Application of Stone Hair Dye on Experimental Animals

Authors: Hatem Abdel Moniem Ahmed, Ragaa Mohamed Abdel Maaboud, Heba A. Mubarak

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A commercially available Stone Hair Dye (SHD) was spread in Upper Egypt and used for dying woman's hair. Paraphenyl-diamine (PPD) is the main component of SHD and reported as a toxic substance. This work aims to study the systemic effects induced in experimental animals as a result of dermal application of SHD. 21 rats were divided into three groups, and doses of SHD and PPD were applied according to body weight (25 mg/100 g body weight) for 90 days. The results revealed that insignificant decrease in RBC count and Hb level, but there were significant increases in the WBC count, AST, ALT, GPT, and total protein while creatinine level was insignificantly increased. Hepatocytes showed a lot of degenerative changes in the form of vacuolated cytoplasm and irregular deeply stained nuclei with vascular congestion and lymphocytic infiltration, while renal affection indicated the occurrence of atrophy of glomerular capillaries, hyperplasia, and widening of bowman space.

Keywords: PPD, SHD, rats and histology, biochemistry and hematology

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11178 Preparation and Characterization of Water-in-Oil Nanoemulsion of 5-Fluorouracil to Enhance Skin Permeation for Treatment of Skin Diseases.

Authors: P. S. Rajinikanth, Shobana Mariappan, Jestin Chellian

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The objective of the study was to prepare and characterize a water-in-oil nano emulsion of 5-Fluorouracil (5FU) to enhance the skin penetration. The present study describes a nano emulsion of 5FU using Capyrol PGMC, Transcutol HP and PEG 400 as oil, surfactant and co-surfactant, respectively. The optimized formulations were further evaluated for heating cooling cycle, centrifugation studies, freeze thaw cycling, particle size distribution and zeta potential in order to confirm the stability of the optimized nano emulsions. The in-vitro characterization results showed that the droplets of prepared formulation were ~100 nm with ± 15 zeta potential. In vitro skin permeation studies was conducted in albino mice skin. Significant increase in permeability parameters was also observed in nano emulsion formulations (P<0.05). The steady-state flux (Jss), enhancement ration and permeability coefficient (Kp) for optimized nano emulsion formulation (FU2, FU1, 1:1 S mix were found to be 24.21 ±2.45 μg/cm2/h, 3.28±0.87 & 19.52±1.87 cm/h, respectively), which were significant compared with conventional gel. The in vitro and in vivo skin deposition studies in rat indicated that the amount of drug deposited from the nano emulsion (292.45 µg/cm2) in skin was significant (P<0.05) an increased as compared to a conventional 5FU gel (121.42 µg/cm2). The skin irritation study using rat skin showed that the mean irritation index of the nano emulsion reduced significantly (P<0.05) as compared with conventional gel contain 1% 5FU. The results from this study suggest that a water-in-oil nano emulsion could be safely used to promote skin penetration of 5FU following topical application.

Keywords: nano emulsion, controlled release, 5 fluorouracil, skin penetration, skin irritation

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11177 Mechanical Properties of Young and Senescence Fibroblast Cells Using Passive Microrheology

Authors: Samira Khalaji, , Fenneke Klein Jan, Kay-E. Gottschalk, Eugenia Makrantonaki, Karin Scharffetter-Kochanek

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Biological aging is a multi-dimensional process that takes place over a whole range of scales from the nanoscopic alterations within individual cells, over transformations in tissues and organs and to changes of the whole organism. On the single cell level, aging involves mutation of genes, differences in gene expression levels as well as altered posttranslational modifications of proteins. A variety of proteins is affected, including proteins of the cell cytoskeleton and migration machinery. Previous work quantified the expression of cytoskeleton proteins on the gene and protein levels in senescent and young fibroblasts. Their results show that senescent skin fibroblasts have an upregulated expression of the intermediate filament (IF) protein vimentin in contrast to actin and tubulin, which are downregulated. IFs play an important role in providing mechanical stability of cells. However, the mechanical properties of IFs depending on cellular senescence or age of the donor has not been studied so far. Hence, we employed passive microrheology on primary human dermal fibroblasts from female donors with age of 28 years (young) and 86 years (old) as model of in vivo aging and human normal dermal fibroblast from 11-year old male with CPD 17-35 (young) and CPD 58-59 (senescence) as a model of in vitro replicative senescence. In contrast to the expectations, our primary results show no significant differences in the viscoelastic properties of fibroblasts depending on age of the donor or cellular replicative senescence.

Keywords: aging, cytoskeleton, fibroblast, mechanical properties

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11176 Hyaluronan and Hyaluronan-Associated Genes in Human CD8 T Cells

Authors: Emily Schlebes, Christian Hundhausen, Jens W. Fischer

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The glycosaminoglycan hyaluronan (HA) is a major component of the extracellular matrix, typically produced by fibroblasts of the connective tissue but also by immune cells. Here, we investigated the capacity of human peripheral blood CD8 T cells from healthy donors to produce HA and to express HA receptors as well as HA degrading enzymes. Further, we evaluated the effect of pharmacological HA inhibition on CD8 T cell function. Using immunocytochemistry together with quantitative PCR analysis, we found that HA synthesis is rapidly induced upon antibody-induced T cell receptor (TCR) activation and almost exclusively mediated by HA synthase 3 (HAS3). TCR activation also resulted in the upregulation of HA receptors CD44, hyaluronan-mediated motility receptor (HMMR), and layilin (LAYN), although kinetics and strength of expression varied greatly between subjects. The HA-degrading enzymes HYAL1 and HYAL2 were detected at low levels and induced by cell activation in some individuals. Interestingly, expression of HAS3, HA receptors, and hyaluronidases were modulated by the proinflammatory cytokines IL-6 and IL-1bβ in most subjects. To assess the functional role of HA in CD8 T cells, we performed carboxyfluorescein succinimidyl ester (CFSE) based proliferation assays and cytokine analysis in the presence of the HA inhibitor 4- Methylumbelliferone (4-MU). Despite significant inter-individual variation with regard to the effective dose, 4-MU resulted in the inhibition of CD8 T cell proliferation and reduced release of TNF-α and IFN-γ. Collectively, these data demonstrate that human CD8 T cells respond to TCR stimulation with a synthesis of HA and expression of HA-related genes. They further suggest that HA inhibition may be helpful in interfering with pathogenic T cell activation in human disease.

Keywords: CD8 T cells, extracellular matrix, hyaluronan, hyaluronan synthase 3

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11175 Sesamol Decreases Melanin Biosynthesis via Melanogenesis-Related Gene Expressions in Melan-a Cells

Authors: Seung-Hwa Baek, In-Jung Nam, Sang-Han Lee

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The development of anti-melanogenic agents is important for the prevention of serious esthetic problem like a melasma, freckle, age spots, and chloasma. The aim of this study was to investigate the anti-melanogenic effect of sesamol, an active lignan isolated from sesame seed, by mushroom and cellular tyrosinase assay, melanin content and the analysis of melanogensis-related mRNA expressions in melana cells. Sesamol showed strong inhibitory activity against the mushroom tyrosinase in a dose-dependent manner. Intracellular tyrosinase inhibition activity was also confirmed by zymography. At a concentration of 50 μM, sesamol inhibited melanin production in melan-a cells with no cytoxicity while those of phenylthiourea (PTU) as a positive control were the same condition. Sesamol significantly inhibited the expression of melanogensis-related genes, such as tyrosinase, tyrosinase-related protein-1 (TRP-1), dopachrome tautomerase (Dct), microphthalmia-associated transcription factor (MITF) and melanocortin 1 receptor (MC1R). These findings indicate that sesamol could reduce melanin biosynthesis via the downregulation of tyrosinase activity and melanin production via subsequent gene expression of melanogenesis-related proteins. Together, these results suggest that the sesamol have strong potential in inhibiting melanin biosynthesis, in that the substance may be used as a new skin-whitening agent of cosmetic materials.

Keywords: sesamol, sesame seed, melanin biosynthesis, melanogenesis-related gene, skin-whitening agent

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11174 Applications of Copper Sensitive Fluorescent Dye to the Studies of the Role of Copper in Cisplatin Resistance in Human Cancer

Authors: Sumayah Mohammed Asiri A., Aviva Levina B., Elizabeth New C., Peter Lay D.

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Pt compounds have been among the most successful anticancer drugs in the last 40 years, but the development of resistance to them is an increasing problem. Cellular homeostasis of an essential metal, Cu, is known to be involved in Pt resistance, but mechanisms of this process are poorly understood. We used a novel ratiometric Cu(I)-sensitive fluorescent probeInCCu1 dye to detect Cu(I) in the mitochondria. Total Cu and labile Cu pool measured using AAS and InCCu1 dye in A2780 cells and their corresponding resistant cells A2780-cis.R cells treated with Cu and cisplatin. The main difference between both cell lines in the presence and absence of Cu(II) is that resistant cells have lower total Cu content but higher labile Cu levels than cisplatin-sensitive cells. This means that resistant cells can metabolize and export excess Cu more efficiently. Furthermore, InCCu1 has emerged not only as an indicator of labile cellular Cu levels in the mitochondria but as a potentially versatile multi-organelle probe.

Keywords: AAS and ICPMS, A2780 and its resistant cells, ratiometric fluorescent sensors, inCCu1, and total and labile Cu

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11173 Clinical Factors of Quality Switched Ruby Laser Therapy for Lentigo Depigmentation

Authors: SunWoo Lee, TaeBum Lee, YoonHwa Park, YooJeong Kim

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Solar lentigines appear predominantly on chronically sun-exposed areas of skin, such as the face and the back of the hands. Among the several ways to lentigines treatment, quality-switched lasers are well-known effective treatment for removing solar lentigines. The present pilot study was therefore designed to assess the efficacy of quality-switched ruby laser treatment of such lentigines compare between pretreatment and posttreatment of skin brightness. Twenty-two adults with chronic sun-damaged skin (mean age 52.8 years, range 37–74 years) were treated at the Korean site. A 694 nm Q-switched ruby laser was used, with the energy density set from 1.4 to 12.5 J/cm2, to treat solar lentigines. Average brightness of skin color before ruby laser treatment was 137.3 and its skin color was brightened after ruby laser treatment by 150.5. Also, standard deviation of skin color was decreased from 17.8 to 16.4. Regarding the multivariate model, age and energy were identified as significant factors for skin color brightness change in lentigo depigmentation by ruby laser treatment. Their respective odds ratios were 1.082 (95% CI, 1.007–1.163), and 1.431 (95% CI, 1.051–1.946). Lentigo depigmentation treatment using ruby lasers resulted in a high performance in skin color brightness. Among the relative factors involve with ruby laser treatment, age and energy were the most effective factors which skin color change to brighter than pretreatment.

Keywords: depigmentation, lentigine, quality switched ruby laser, skin color

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11172 Cytotoxicity of Nano β–Tricalcium Phosphate (β-TCP) on Human Osteoblast (hFOB1.19)

Authors: Jer Ping Ooi, Shah Rizal Bin Kasim, Nor Aini Saidin

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The objective of this study was to synthesize nano-sized β-tricalcium phosphate (β-TCP) powder and assess its cytotoxic effects on human osteoblast (hFOB1.19) by using four cytotoxicity assays, namely, lactose dehydrogenase (LDHe), tetrazolium hydroxide (XTT), neutral red (NR), and sulforhodamine B (SRB) assays. β-tricalcium phosphate (β-TCP) is a calcium phosphate compound commonly used as an implant material. To date, bulk-sized β-TCP is reported to be readily tolerated by the osteogenic cells and body based on in vitro, in vivo experiments and clinical studies. However, to what extent of nano-sized β-TCP will react in models as compared to bulk β-TCP is yet to be investigated. Thus, in this project, the cells were treated with nano β-TCP powder within a range of concentrations from 0 to 1000 μg/mL for 24, 48, and 72 h. The cytotoxicity tests showed that loss of cell viability ( > 50%) was high for hFOB1.19 cells in all assays. Cell cycle and apoptosis analysis of hFOB1.19 cells revealed that 50 μg/mL of the compound led to 30.5% of cells being apoptotic after 72 h of incubation, and the percentage was increased to 58.6% when the concentration was increased to 200 μg/mL. When the incubation time was increased from 24 to 72 h, the percentage of apoptotic cells increased from 17.3% to 58.6% when the hFOB1.19 were exposed with 200 μg/mL of nano β-TCP powder. Thus, both concentration and exposure duration affected the cytotoxicity effects of the nano β-TCP powder on hFOB1.19. We hypothesize that these cytotoxic effects on hFOB1.19 are related to the nano-scale size of the β-TCP.

Keywords: β-tricalcium phosphate, hFOB1.19, adipose-derived mesenchymal stem cells, cytotoxicity

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11171 Nurses’ Perception of Pain and Skin Tearing during Dressing Change

Authors: Jung Yoon Kim

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Introduction: Wounds inevitably cause patients to experience discomfort, distress, and consequentially reduced quality of life due to entailed pain, maceration, and foul odor. The dressing has been a universal wound care method in which wounds are covered and protected, and an optimum environment for healing is provided. This study aimed to investigate Korean nurses’ level of awareness of pain and skin tearing in wound beds and/or peri-wound skin at dressing change. Methods: A descriptive study was performed. Convenience sampling was employed, and registered nurses were recruited from attendees of continuing education program. A total of 399 participants (RN) completed the questionnaire. Data were collected from September to November 2022. Results: Many of them perceived skin tearing and wound-related pain associated with dressing changes, but most of them did not assess and record pain and skin tearing at dressing change. More than half of the respondents reported that they did not provide nursing intervention to prevent pain and skin tearing. Many of them reported that a systematic educational program for preventing pain and skin tearing at dressing changes was needed. Discussion: Many of the respondents were aware of pain and skin tearing at dressing change but did not take any further necessary measures, including nursing intervention, for the most appropriate, systematic pain and skin tearing management. Therefore, this study suggested that a systematic and comprehensive educational program for Korean healthcare professionals needs to be developed and implemented in Korea’s hospital settings.

Keywords: skin tearing, pain, dressing change, nurses

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11170 Analysis of Cell Cycle Status in Radiation Non-Targeted Hepatoma Cells Using Flow Cytometry: Evidence of Dose Dependent Response

Authors: Sharmi Mukherjee, Anindita Chakraborty

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Cellular irradiation incites complex responses including arrest of cell cycle progression. This article accentuates the effects of radiation on cell cycle status of radiation non-targeted cells. Human Hepatoma HepG2 cells were exposed to increasing doses of γ radiations (1, 2, 4, 6 Gy) and their cell culture media was transferred to non-targeted HepG2 cells cultured in other Petri plates. These radiation non-targeted cells cultured in the ICCM (Irradiated cell conditioned media) were the bystander cells on which cell cycle analysis was performed using flow cytometry. An apparent decrease in the distribution of bystander cells at G0/G1 phase was observed with increased radiation doses upto 4 Gy representing a linear relationship. This was accompanied by a gradual increase in cellular distribution at G2/M phase. Interestingly the number of cells in G2/M phase at 1 and 2 Gy irradiation was not significantly different from each other. However, the percentage of G2 phase cells at 4 and 6 Gy doses were significantly higher than 2 Gy dose indicating the IC50 dose to be between 2 and 4 Gy. Cell cycle arrest is an indirect indicator of genotoxic damage in cells. In this study, bystander stress signals through the cell culture media of irradiated cells disseminated the radiation induced DNA damages in the non-targeted cells which resulted in arrest of the cell cycle progression at G2/M phase checkpoint. This implies that actual radiation biological effects represent a penumbra with effects encompassing a larger area than the actual beam. This article highlights the existence of genotoxic damages as bystander effects of γ rays in human Hepatoma cells by cell cycle analysis and opens up avenues for appraisal of bystander stress communications between tumor cells. Contemplation of underlying signaling mechanisms can be manipulated to maximize damaging effects of radiation with minimum dose and thus has therapeutic applications.

Keywords: bystander effect, cell cycle, genotoxic damage, hepatoma

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11169 Antibacterial Hydrogels for Wound Care

Authors: Saba Atefyekta

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Aim: Control of bacterial bioburden in wounds is an important step for minimizing the risk of wound infection. An antimicrobial hydrogel wound dressing is developed out of soft polymeric hydrogels that contain antimicrobial peptides (AMPs). Such wound dressings can bind and kill all types of bacteria, even the resistance types at the wound site. Methods: AMPs are permanently bonded onto a soft nanostructured polymer via covalent attachment and physical entanglement. This improves stability, rapid antibacterial activity, and, most importantly, prevents the leaching of AMPs. Major Findings: Antimicrobial analysis of antimicrobial hydrogels using in-vitro wound models confirmed >99% killing efficiency against multiple bacterial trains, including MRSA, MDR, E. Coli. Furthermore, the hydrogel retained its antibacterial activity for up to 4 days when exposed to human serum. Tests confirmed no release of AMPs, and it was proven non-toxic to mammalian cells. An in-vivo study on human intact skin showed a significant reduction of bacteria for part of the subject’s skin treated with antibacterial hydrogels. A similar result was detected through a qualitative study in veterinary trials on different types of surgery wounds in cats, dogs, and horses. Conclusions: Antimicrobial hydrogels wound dressings developed by permanent attachment of AMPs can effectively and rapidly kill bacteria in contact. Such antibacterial hydrogel wound dressings are non-toxic and do not release any substances into the wound.

Keywords: antibacterial wound dressing, antimicrobial peptides, post-surgical wounds, infection

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11168 How to Prevent From Skin Complications in Diabetes Type 2 in View Point of Student of Shiraz University of Medical Sciences

Authors: Zahra Abdi, Roghayeh Alipour, Babak Farahi Ghasraboonasr

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Introduction: Diabetes is a serious medical condition that requires constant care. People with type 2 diabetes may also be likely to experience dry, itchy skin and poor wound healing. Some people with diabetes will have a skin problems at some time in their lives and for those not yet diagnosed with diabetes, a skin problem can be an indication of the disease. our purpose was to assess the capability and knowledge of students of Shiraz University of Medical Sciences about prevent from skin complications in diabetes type 2. Methods: In this descriptive cross-sectional study, knowledge of 360 students of Shiraz University of Medical Sciences was evaluated about different ways to avoid skin complications in diabetes type 2. Data were analyzed by spss19.(P<0.05) was considered significant. Results: 360 students of Shiraz University of Medical Sciences participated in this study. 45% of students agree with the effect of Moisturize skin daily, If Diabetics have sensitive skin, choose a fragrance-free, dye-free moisturizer that won’t irritate skin. 52% believe that Protect skin from sun can be so useful, Sun exposure is drying and aging. Use sunscreen with SPF 30 or higher whenever you’re outside. Wear gloves when doing yardwork to protect the skin on your hands. 62% of students strongly agree with Carefully clean any cuts and scrapes, If diabetics notice any sign of infection skin that’s red, swollen, or warm to the touch, or has a foul-smelling drainage or pus should consulting with a doctor immediately. Diabetics should be careful about any injury that takes longer than normal to heal and they should consulting with doctor about them too. 72% of students believe that diabetics should be diligent about daily foot care. Clean and moisturize feet each day and check each foot closely, top and bottom, for wounds even a tiny cut, blisters, or cracked skin. Conclusions: The risk of getting these diabetes complications can be lessened by controlling blood sugar. Skin complications can cause serious consequences. Taking care of skin is so important and using these tips are remarkable effective and help diabetics to look after their skin easier.

Keywords: skin complications, diabetes type 2, Shiraz University of Medical Sciences, diabetics

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11167 Histamine Skin Reactivity Increased with Body Mass Index in Korean Children

Authors: Jeong Hong Kim, Ju Wan Kang

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Objective: Histamine skin prick testing is most commonly used to diagnose immunoglobulin E (IgE)-mediated allergic diseases, and histamine reactivity is used as a standardized positive control in the interpretation of a skin prick test. However, reactivity to histamine differs among individuals for reasons that are poorly understood. The present study aimed to evaluate the potential association between body mass index (BMI) and histamine skin reactivity in children. Methods: A total of 451 children (246 boys, 205 girls) aged 7–8 years were enrolled in this study. The skin prick test was performed with 26 aeroallergens commonly found in Korea. Other information was collected, including sex, age, BMI, parental allergy history, and parental smoking status. Multivariate analysis was used to confirm the association between histamine skin reactivity and BMI. Results: The histamine wheal size was revealed to be associated with BMI (Spearman's Rho 0.161, p < 0.001). This association was confirmed by multivariate analysis, after adjusting for sex, age, parental allergy history, parental smoking status, and allergic sensitization (coefficient B 0.071, 95% confidence interval 0.030–0.112). Conclusions: Skin responses to histamine were primarily correlated with increased BMI. Further studies are needed to understand the clinical implication of BMI when interpreting the results of skin prick test.

Keywords: allergy, body mass index, histamine, skin prick test

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11166 Proinflammatory Response of Agglomerated TiO2 Nanoparticles in Human-Immune Cells

Authors: Vaiyapuri Subbarayn Periasamy, Jegan Athinarayanan, Ali A. Alshatwi

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The widespread use of Titanium oxide nanoparticles (TiO2-NPs), now are found with different physic-chemical properties (size, shape, chemical properties, agglomeration, etc.) in many processed foods, agricultural chemicals, biomedical products, food packaging and food contact materials, personal care products, and other consumer products used in daily life. Growing evidences have been highlighted that there are risks of physico-chemical properties dependent toxicity with special attention to “TiO2-NPs and human immune system”. Unfortunately, agglomeration and aggregation have frequently been ignored in immuno-toxicological studies, even though agglomeration and aggregation would be expected to affect nanotoxicity since it changes the size, shape, surface area, and other properties of the TiO2-NPs. In this present investigation, we assessed the immune toxic effect of TiO2-NPs on human immune cells Total WBC including Lymphocytes (T cells (CD3+), T helper cells (CD3+, CD4+), Suppressor/cytotoxic T cells (CD3+/CD8+) and NK cells (CD3-/CD16+ and CD56+), Monocytes (CD14+, CD3-) and B lymphocytes (CD19+, CD3-) in order to find the immunological response (IL1A, IL1B, IL2 IL-4, IL5 IL-6, IL-10, IL-12, IL-13, IFN-γ, TGF-β, and TNF-a) and redox gene regulation (TNF, p53, BCl-2, CAT, GSTA4, TNF, CYP1A, POR, SOD1, GSTM3, GPX1, and GSR1)-linking physicochemical properties with special reference to agglomeration of TiO2-NPs. Our findings suggest that TiO2-NPs altered cytokine production, enhanced phagocytic indexing, metabolic stress through specific immune regulatory- genes expression in different WBC subsets and may contribute to pro-inflammatory response. Although TiO2-NPs have great advantages in the personal care products, biomedical, food and agricultural products, its chronic and acute immune-toxicity still need to be assessed carefully with special reference to food and environmental safety.

Keywords: TiO2 nanoparticles, oxidative stress, cytokine, human immune cells

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11165 In vitro Regeneration of Neural Cells Using Human Umbilical Cord Derived Mesenchymal Stem Cells

Authors: Urvi Panwar, Kanchan Mishra, Kanjaksha Ghosh, ShankerLal Kothari

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Background: Day-by-day the increasing prevalence of neurodegenerative diseases have become a global issue to manage them by medical sciences. The adult neural stem cells are rare and require an invasive and painful procedure to obtain it from central nervous system. Mesenchymal stem cell (MSCs) therapies have shown remarkable application in treatment of various cell injuries and cell loss. MSCs can be derived from various sources like adult tissues, human bone marrow, umbilical cord blood and cord tissue. MSCs have similar proliferation and differentiation capability, but the human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are proved to be more beneficial with respect to cell procurement, differentiation to other cells, preservation, and transplantation. Material and method: Human umbilical cord is easily obtainable and non-controversial comparative to bone marrow and other adult tissues. The umbilical cord can be collected after delivery of baby, and its tissue can be cultured using explant culture method. Cell culture medium such as DMEMF12+10% FBS and DMEMF12+Neural growth factors (bFGF, human noggin, B27) with antibiotics (Streptomycin/Gentamycin) were used to culture and differentiate mesenchymal stem cells into neural cells, respectively. The characterisations of MSCs were done with Flow Cytometer for surface markers CD90, CD73 and CD105 and colony forming unit assay. The differentiated various neural cells will be characterised by fluorescence markers for neurons, astrocytes, and oligodendrocytes; quantitative PCR for genes Nestin and NeuroD1 and Western blotting technique for gap43 protein. Result and discussion: The high quality and number of MSCs were isolated from human umbilical cord via explant culture method. The obtained MSCs were differentiated into neural cells like neurons, astrocytes and oligodendrocytes. The differentiated neural cells can be used to treat neural injuries and neural cell loss by delivering cells by non-invasive administration via cerebrospinal fluid (CSF) or blood. Moreover, the MSCs can also be directly delivered to different injured sites where they differentiate into neural cells. Therefore, human umbilical cord is demonstrated to be an inexpensive and easily available source for MSCs. Moreover, the hUCMSCs can be a potential source for neural cell therapies and neural cell regeneration for neural cell injuries and neural cell loss. This new way of research will be helpful to treat and manage neural cell damages and neurodegenerative diseases like Alzheimer and Parkinson. Still the study has a long way to go but it is a promising approach for many neural disorders for which at present no satisfactory management is available.

Keywords: bone marrow, cell therapy, explant culture method, flow cytometer, human umbilical cord, mesenchymal stem cells, neurodegenerative diseases, neuroprotective, regeneration

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11164 Treating Complex Pain and Addictions with Bioelectrode Therapy: An Acupuncture Point Stimulus Method for Relieving Human Suffering

Authors: Les Moncrieff

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In a world awash with potent opioids flaming an international crisis, the need to explore safe alternatives has never been more urgent. Bio-electrode Therapy is a novel adjunctive treatment method for relieving acute opioid withdrawal symptoms and many types of complex acute and chronic pain (often the underlying cause of opioid dependence). By combining the science of developmental bioelectricity with Traditional Chinese Medicine’s theory of meridians, rapid relief from pain is routinely being achieved in the clinical setting. Human body functions are dependent on electrical factors, and acupuncture points on the body are known to have higher electrical conductivity than surrounding skin tissue. When tiny gold- and silver-plated electrodes are secured to the skin at specific acupuncture points using established Chinese Medicine principles and protocols, an enhanced microcurrent and electrical field are created between the electrodes, influencing the entire meridian and connecting meridians. No external power source or electrical devices are required. Endogenous DC electric fields are an essential fundamental component for development, regeneration, and wound healing. Disruptions in the normal ion-charge in the meridians and circulation of blood will manifest as pain and development of disease. With the application of these simple electrodes (gold acting as cathode and silver as anode) according to protocols, the resulting microcurrent is directed along the selected meridians to target injured or diseased organs and tissues. When injured or diseased cells have been stimulated by the microcurrent and electrical fields, the permeability of the cell membrane is affected, resulting in an immediate relief of pain, a rapid balancing of positive and negative ions (sodium, potassium, etc.) in the cells, the restoration of intracellular fluid levels, replenishment of electrolyte levels, pH balance, removal of toxins, and a re-establishment of homeostasis.

Keywords: bioelectricity, electrodes, electrical fields, acupuncture meridians, complex pain, opioid withdrawal management

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11163 Trans-Activator of Transcription-Tagged Active AKT1 Variants for Delivery to Mammalian Cells

Authors: Tarana Siddika, Ilka U. Heinemann, Patrick O’Donoghue

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Protein kinase B (AKT1) is a serine/threonine kinase and central transducer of cell survival pathways. Typical approaches to study AKT1 biology in cells rely on growth factor or insulin stimulation that activates AKT1 via phosphorylation at two key regulatory sites (Threonine308, Serine473), yet cell stimulation also activates many other kinases and fails to differentiate the effect of the two main activating sites of AKT1 on downstream substrate phosphorylation and cell growth. While both AKT1 activating sites are associated with disease and used as clinical markers, in some cancers, high levels of Threonine308 phosphorylation are associated with poor prognosis while in others poor survival correlates with high Serine473 levels. To produce cells with specific AKT1 activity, a system was developed to deliver active AKT1 to human cells. AKT1 phospho-variants were produced from Escherichia coli with programmed phosphorylation by genetic code expansion. Tagging of AKT1 with an N-terminal cell penetrating peptide tag derived from the human immunodeficiency virus trans-activator of transcription (TAT) helped to enter AKT1 proteins in mammalian cells. The TAT-tag did not alter AKT1 kinase activity and was necessary and sufficient to rapidly deliver AKT1 protein variants that persisted in human cells for 24 h without the need to use transfection reagents. TAT-pAKT1T308, TAT-pAKT1S473 and TAT-pAKT1T308S473 proteins induced selective phosphorylation of the known AKT1 substrate GSK-3αβ, and downstream stimulation of the AKT1 pathway as evidenced by phosphorylation of ribosomal protein S6 at Serine240/244 in transfected cells. Increase in cell growth and proliferation was observed due to the transfection of different phosphorylated AKT1 protein variants compared to cells with TAT-AKT1 protein. The data demonstrate efficient delivery of AKT1 with programmed phosphorylation to human cells, thus establishing a cell-based model system to investigate signaling that is dependent on specific AKT1 activity and phosphorylation.

Keywords: cell penetrating peptide, cell signaling, protein kinase b (AKT1), phosphorylation

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11162 Cosmetic Recommendation Approach Using Machine Learning

Authors: Shakila N. Senarath, Dinesh Asanka, Janaka Wijayanayake

Abstract:

The necessity of cosmetic products is arising to fulfill consumer needs of personality appearance and hygiene. A cosmetic product consists of various chemical ingredients which may help to keep the skin healthy or may lead to damages. Every chemical ingredient in a cosmetic product does not perform on every human. The most appropriate way to select a healthy cosmetic product is to identify the texture of the body first and select the most suitable product with safe ingredients. Therefore, the selection process of cosmetic products is complicated. Consumer surveys have shown most of the time, the selection process of cosmetic products is done in an improper way by consumers. From this study, a content-based system is suggested that recommends cosmetic products for the human factors. To such an extent, the skin type, gender and price range will be considered as human factors. The proposed system will be implemented by using Machine Learning. Consumer skin type, gender and price range will be taken as inputs to the system. The skin type of consumer will be derived by using the Baumann Skin Type Questionnaire, which is a value-based approach that includes several numbers of questions to derive the user’s skin type to one of the 16 skin types according to the Bauman Skin Type indicator (BSTI). Two datasets are collected for further research proceedings. The user data set was collected using a questionnaire given to the public. Those are the user dataset and the cosmetic dataset. Product details are included in the cosmetic dataset, which belongs to 5 different kinds of product categories (Moisturizer, Cleanser, Sun protector, Face Mask, Eye Cream). An alternate approach of TF-IDF (Term Frequency – Inverse Document Frequency) is applied to vectorize cosmetic ingredients in the generic cosmetic products dataset and user-preferred dataset. Using the IF-IPF vectors, each user-preferred products dataset and generic cosmetic products dataset can be represented as sparse vectors. The similarity between each user-preferred product and generic cosmetic product will be calculated using the cosine similarity method. For the recommendation process, a similarity matrix can be used. Higher the similarity, higher the match for consumer. Sorting a user column from similarity matrix in a descending order, the recommended products can be retrieved in ascending order. Even though results return a list of similar products, and since the user information has been gathered, such as gender and the price ranges for product purchasing, further optimization can be done by considering and giving weights for those parameters once after a set of recommended products for a user has been retrieved.

Keywords: content-based filtering, cosmetics, machine learning, recommendation system

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11161 Wound Healing Potential and Comparison of Mummy Substance Effect on Adipose and Wharton’s Jelly-Derived Mesenchymal Stem Cells Co-Cultured with Human Fibroblast

Authors: Sepideh Hassanpour Khodaei

Abstract:

Background/Objectives: The purpose of this study is to evaluate the effect of mummy substances on two issues of proliferation and production of matrix protein synthesis in wound healing. Methods: The methodology used for this aim involves isolating mesenchymal stem cells and human fibroblasts procured at Pastor Institute, Iran. The cells were treated with mummy substances separately and co-cultured between ASCs and WJSCs, and fibroblasts. Proliferation was assessed by Ki67 method in monolayer conditions. Synthesis of components of extracellular matrix (ECM) such as collagen type I, type III, and fibronectin 1 (FN1) was determined by qPCR. Results: The effects of adipocyte stem cells (ASCs), Wharton Jelly Stem Cells (WJSCs), and Mummy material on fibroblast proliferation and migration were evaluated. The present finding underlined the importance of Mummy material, ASCs, and WJSCs in the proliferation and migration of fibroblast cells. Furthermore, the expression of collagen I, III, and FN1 was increased in the presence of the above material and cells. Conclusion: This study presented an effective in vitro method for the healing process. Hence, the prospect of utilizing Mummy material and stem cell-based therapies in wound healing as a therapeutic approach is promising.

Keywords: mummy material, wound healing, adipose tissue, Wharton’s jelly

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11160 Cytotoxicity of Thymoquinone Alone or in Combination with Cisplatin (CDDP) Against Oral Squamous Cell Carcinoma in Vitro

Authors: Omar M. Al Aufi, Abdulwahab Noorwali, Ahmed Al Abd, Safia Alattas, Fathya Zahran, Fahd Almutairi

Abstract:

Cisplatin (CDDP) is a potent anticancer agent used for several tumor types. Thymoquinone (TQ) is a naturally occurring compound drawing great attention as an anticancer and chemomodulator for chemotherapies. Herein, we studied the potential cytotoxicity of thymoquinone, CDDP and their combination against human oral squamous cell carcinoma cells in contrast to normal oral epithelial cells. CDDP similarly killed both head and neck squamous cell carcinoma cells (UMSCC-14C) and normal oral epithelial cells (OEC). TQ alone exerted considerable cytotoxicity against UMSCC-14C cells, while it induced a weaker killing effect against normal oral epithelial cells (OEC). The equitoxic combination of TQ and CDDP showed additive to synergistic interaction against both UMSCC-14C and OEC cells. TQ alone increased apoptotic cell fraction in UMSCC-14C cells as early as after 6 hours. In addition, prolonged exposure of UMSCC-14C to TQ alone resulted in 96.7±1.6% total apoptosis, which was increased after combination with CDDP to 99.3±1.2% in UMSCC-14C cells. On the other hand, TQ induced a marginal increase in the apoptosis in OEC and even decreased the apoptosis induced by CDDP alone. Finally, apoptosis induction results were confirmed by the change in the expression levels of p53, Bcl-2 and Caspase-9 proteins in both UMSCC-14c and OEC cells.

Keywords: thymoquinone, cisplatin, apoptosis, oral squamous cell carcinoma, P53, Caspase-9, Bcl-2

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11159 Human 3D Metastatic Melanoma Models for in vitro Evaluation of Targeted Therapy Efficiency

Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

Abstract:

Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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11158 Behavior of hFOB 1.19 Cells in Injectable Scaffold Composing of Pluronic F127 and Carboxymethyl Hexanoyl Chitosan

Authors: Lie-Sian Yap, Ming-Chien Yang

Abstract:

This study demonstrated a novel injectable hydrogel scaffold composing of Pluronic F127, carboxymethyl hexanoyl chitosan (CA) and glutaraldehyde (GA) for encapsulating human fetal osteoblastic cells (hFOB) 1.19. The hydrogel was prepared by mixing F127 and GA in CA solution at 4°C. The mechanical properties and cytotoxicity of this hydrogel were determined through rheological measurements and MTT assay, respectively. After encapsulation process, the hFOB 1.19 cells morphology was examined using fluorescent and confocal imaging. The results indicated that the Tgel of this system was around 30°C, where sol-gel transformation occurred within 90s and F127/CA/GA gel was able to remain intact in the medium for more than 1 month. In vitro cell culture assay revealed that F127/CA/GA hydrogels were non-cytotoxic. Encapsulated hFOB 1.19 cells not only showed the spherical shape and formed colonies, but also reduced their size. Moreover, the hFOB 1.19 cells showed that cells remain alive after the encapsulation process. Based on these results, these F127/CA/GA hydrogels can be used to encapsulate cells for tissue engineering applications.

Keywords: carboxymethyl hexanoyl chitosan, cell encapsulation, hFOB 1.19, Pluronic F127

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11157 Analysis of Sweat Evaporation and Heat Transfer on Skin Surface: A Pointwise Numerical Study

Authors: Utsav Swarnkar, Rabi Pathak, Rina Maiti

Abstract:

This study aims to investigate the thermoregulatory role of sweating by comprehensively analyzing the evaporation process and its thermal cooling impact on local skin temperature at various time intervals. Traditional experimental methods struggle to fully capture these intricate phenomena. Therefore, numerical simulations play a crucial role in assessing sweat production rates and associated thermal cooling. This research utilizes transient computational fluid dynamics (CFD) to enhance our understanding of the evaporative cooling process on human skin. We conducted a simulation employing the k-w SST turbulence model. This simulation includes a scenario where sweat evaporation occurs over the skin surface, and at particular time intervals, temperatures at different locations have been observed and its effect explained. During this study, sweat evaporation was monitored on the skin surface following the commencement of the simulation. Subsequent to the simulation, various observations were made regarding temperature fluctuations at specific points over time intervals. It was noted that points situated closer to the periphery of the droplets exhibited higher levels of heat transfer and lower temperatures, whereas points within the droplets displayed contrasting trends.

Keywords: CFD, sweat, evaporation, multiphase flow, local heat loss

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11156 Comparative Stem Cells Therapy for Regeneration of Liver Fibrosis

Authors: H. M. Imam, H. M. Rezk, A. F. Tohamy

Abstract:

Background: Human umbilical cord blood (HUCB) is considered as a unique source for stem cells. HUCB contain different types of progenitor cells which could differentiate into hepatocytes. Aims: To investigate the potential of rat's liver damage repair using human umbilical cord mesenchymal stem cells (hUCMSCs). We investigated the feasibility for hUCMSCs in recovery from liver damage. Moreover, investigating fibrotic liver repair and using the CCl4-induced model for liver damage in the rat. Methods: Rats were injected with 0.5 ml/kg CCl4 to induce liver damage and progressive liver fibrosis. hUCMSCs were injected into the rats through the tail vein; Stem cells were transplanted at a dose of 1×106 cells/rat after 72 hours of CCl4 injection without receiving any immunosuppressant. After (6 and 8 weeks) of transplantation, blood samples were collected to assess liver functions (ALT, AST, GGT and ALB) and level of Procollagen III as a liver fibrosis marker. In addition, hepatic tissue regeneration was assessed histopathologically and immunohistochemically using antihuman monoclonal antibodies against CD34, CK19 and albumin. Results: Biochemical and histopathological analysis showed significantly increased recovery from liver damage in the transplanted group. In addition, HUCB stem cells transdifferentiated into functional hepatocytes in rats with hepatic injury which results in improving liver structure and function. Conclusion: Our findings suggest that transplantation of hUCMSCs may be a novel therapeutic approach for treating liver fibrosis. Therefore, hUCMSCs are a potential option for treatment of liver cirrhosis.

Keywords: carbon tetra chloride, liver fibrosis, mesenchymal stem cells, rat

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11155 Evaluation of Herbal Extracts for Their Potential Application as Skin Prebiotics

Authors: Anja I. Petrov, Milica B. Veljković, Marija M. Ćorović, Ana D. Milivojević, Milica B. Simović, Katarina M. Banjanac, Dejan I. Bezbradica

Abstract:

One of the fundamental requirements for overall human well-being is a stable and balanced microbiome. Aside from the microorganisms that reside within the body, a large number of microorganisms, especially bacteria, swarming the human skin is in homeostasis with the host and represents a skin microbiota. Even though the immune system of the skin is capable of distinguishing between commensal and potentially harmful transient bacteria, the cutaneous microbial balance can be disrupted under certain circumstances. In that case, a reduction in the skin microbiota diversity, as well as changes in metabolic activity, results in dermal infections and inflammation. Probiotics and prebiotics have the potential to play a significant role in the treatment of these skin disorders. The most common resident bacteria found on the skin, Staphylococcus epidermidis, can act as a potential skin probiotic, contributing to the protection of healthy skin from pathogen colonization, such as Staphylococcus aureus, which is related to atopic dermatitis exacerbation. However, as it is difficult to meet regulations in cosmetic products, another therapy approach could be topical prebiotic supplementation of the skin microbiota. In recent research, polyphenols are attracting scientists' interest as biomolecules with possible prebiotic effects on the skin microbiota. This research aimed to determine how herbal extracts rich in different polyphenolic compounds (lemon balm, St. John's wort, coltsfoot, pine needle, and yarrow) affected the growth of S. epidermidis and S. aureus. The first part of the study involved screening plants to determine if they could be regarded as probable candidates to be skin prebiotics. The effect of each plant on bacterial growth was examined by supplementing the nutrient medium with their extracts and comparing it with control samples (without extract). The results obtained after 24 h of incubation showed that all tested extracts influenced the growth of the examined bacteria to some extent. Since lemon balm and St. John's wort extracts displayed bactericidal activity against S. epidermidis, whereas coltsfoot inhibited both bacteria equally, they were not explored further. On the other hand, pine needles and yarrow extract led to an increase in S. epidermidis/S. aureus ratio, making them prospective candidates to be used as skin prebiotics. By examining the prebiotic effect of two extracts at different concentrations, it was revealed that, in the case of yarrow, 0.1% of extract dry matter in the fermentation medium was optimal, while for the pine needle extract, a concentration of 0.05% was preferred, since it selectively stimulated S. epidermidis growth and inhibited S. aureus proliferation. Additionally, the total polyphenols and flavonoid content of the two extracts were determined, revealing different concentrations and polyphenol profiles. Since yarrow and pine extracts affected the growth of skin bacteria in a dose-dependent manner, by carefully selecting the quantities of these extracts, and thus polyphenols content, it is possible to achieve desirable alterations of skin microbiota composition, which may be suitable for the treatment of atopic dermatitis.

Keywords: herbal extracts, polyphenols, skin microbiota, skin prebiotics

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11154 An Electron Microscopic Study of Developing Human Fetal Pancreas

Authors: Gupta Renu, T. S. Roy

Abstract:

Introduction: For the prospect of successful replacement therapies in treatment of Diabetes mallitus it is necessary to know events occurring during normal human pancreas development. Literature of human pancreas development are few in number as well as mainly related to first trimester because of ethical and technical difficulties. So the study was conducted on 12 fetuses from 12 gestational weeks (GW) to 5 months of infant to know normal development of exocrine and endocrine part of human pancreas. Material and Methods: Human fetalpancreases were screened by haematoxyline and eosin staining and done electron microscopy for suitable specimens to know ultrastructural detail of fetal pancreas. Results:It was observed arborized tubules, the cells budding out from these tubules differentiated into primitive acini and islets in 12thGW. At 14 weeks scanty granules were observed in the endocrine cells which coincided with the capillary invasion of the islets. The ducts and acini were surrounded by well-organized connective tissue. The acinihad elongated cells, small amount of cytoplasm and large open face euchromatic nuclei with single nucleolus. The mature form of islets of Langerhans was observed close to the acini and duct in 20 GW fetus. Connective tissue around the duct was well organized.No significant developmental change was observed early postnatal, infant. Conclusion: The development of both component exocrine as well as endocrine part of human fetal pancreas was studied by light and electron microscopy. Observations suggested that the fetal pancreas contained mainly ducts, few acini, many centroacinar cells, and large undifferentiated tissue.

Keywords: gestational weeks (GW), acini, islets of Langerhans, ducts

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11153 Methotrexate Associated Skin Cancer: A Signal Review of Pharmacovigilance Center

Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

Abstract:

Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

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11152 Chromosomal Damage in Human Lymphocytes by Ultraviolet Radiation

Authors: Felipe Osorio Ospina, Maria Adelaida Mejia Arango, Esteban Onésimo Vallejo Agudelo, Victoria Lucía Dávila Osorio, Natalia Vargas Grisales, Lina María Martínez Sanchez, Camilo Andrés Agudelo Vélez, Ángela Maria Londoño García, Isabel Cristina Ortiz Trujillo

Abstract:

Excessive exposure to ultraviolet radiation, has shown to be a risk factor for photodamage, alteration of the immune mechanisms to recognize malignant cells and cutaneous pro-inflamatorios States and skin cancers. Objective: Identify the time of exposure to ultraviolet radiation for the production of chromosomal damage in human lymphocytes. Methodology: We conducted an in vitro study serial, in which samples were taken from heparinized blood of healthy people, who do not submit exposure to agents that could induce chromosomal alterations. The samples were cultured in RPMI-1640 medium containing 10% fetal bovine serum, penicillin and streptomycin antibiotic. Subsequently, they were grouped and exposed to ultraviolet light for 1 to 20 seconds. At the end of the treatments, cytology samples were prepared, and it was colored with Giemsa (5%). Reading was carried out in an optical microscope and 100 metaphases analysed by treatment for posting chromosomal alterations. Each treatment was conducted at three separate times and each became two replicas. Results: We only presented chromosomal alterations in lymphocytes exposed to UV for a groups 1 to 3 seconds (p<0.05). Conclusions: Exposure to ultraviolet radiation generates visible damage in chromosomes from human lymphocytes observed in light microscopy, the highest rates of injury was observed between two and three seconds, and above this value, the reduction in the number of mitotic cells was evident.

Keywords: ultraviolet rays, lymphocytes, chromosome breakpoints, photodamage

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11151 Ultraviolet Radiation and Chromosomal Damage in Human Lymphocytes

Authors: Felipe Osorio Ospina, Maria Adelaida Mejia Arango, Esteban Onésimo Vallejo Agudelo, Victoria Lucía Dávila Osorio, Natalia Vargas Grisales, Lina María Martínez Sanchez, Camilo Andrés Agudelo Vélez, Ángela Maria Londoño García, Isabel Cristina Ortiz Trujillo

Abstract:

Excessive exposure to ultraviolet radiation, has shown to be a risk factor for photodamage, alteration of the immune mechanisms to recognize malignant cells and cutaneous pro-inflamatorios states and skin cancers. Objective: To identify the time of exposure to ultraviolet radiation for the production of chromosomal damage in human lymphocytes. Methodology: We conducted an in vitro study serial, in which samples were taken from the heparinized blood of healthy people, who do not submit exposure to agents that could induce chromosomal alterations. The samples were cultured in RPMI-1640 medium containing 10% fetal bovine serum, penicillin, and streptomycin antibiotic. Subsequently, they were grouped and exposed to ultraviolet light for 1 to 20 seconds. At the end of the treatments, cytology samples were prepared, and it was colored with Giemsa (5%). Reading was carried out in an optical microscope and 100 metaphases analysed by treatment for posting chromosomal alterations. Each treatment was conducted at three separate times and each became two replicas. Results: We only presented chromosomal alterations in lymphocytes exposed to UV for groups 1 to 3 seconds (p < 0.05). Conclusions: Exposure to ultraviolet radiation generates visible damage in chromosomes from human lymphocytes observed in light microscopy, the highest rates of injury was observed between two and three seconds, and above this value, the reduction in the number of mitotic cells was evident.

Keywords: chromosome breakpoints, lymphocytes, photodamage, ultraviolet rays

Procedia PDF Downloads 551