Search results for: inflammatory cytokines

Authors: Fernando G. Torres, Omar P. Troncoso

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Starch is a highly biocompatible, non-toxic, and biodegradable polymer. It is widely used in biomedical applications, including drug delivery systems and tissue engineering scaffolds. Curcumin, a phenolic compound found in the dried root of Curcuma longa, has been used as a nutritional supplement due to its antimicrobial, anti-inflammatory, and antioxidant effects. However, the major problem with ingesting curcumin by itself is its poor bioavailability due to its poor absorption and rapid metabolism. In this study, we report a novel methodology to prepare starch nanoparticles loaded with curcumin. The nanoparticles were synthesized via nanoprecipitation of starch granules extracted from native Andean potatoes (Solanum tuberosum ssp. and Andigena var Huamantanga varieties). The nanoparticles were crosslinked and stabilized by using sodium tripolyphosphate and Tween®80, respectively. The characterization of the nanoparticles loaded with curcumin was assessed by Fourier Transform Infrared Spectroscopy, Dynamic Light Scattering, Zeta potential, and Differential scanning calorimetry. UV-vis spectrophotometry was used to evaluate the loading efficiency and capacity of the samples. The results showed that native starch nanoparticles could be used to prepare promising nanocarriers for the controlled release of curcumin.

Keywords: starch nanoparticle, nanoprecipitation, curcumin, biomedical applications

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Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

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Introduction: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of unknown cause. Concomitant autoimmune disorders have been described in 30–50% of patients with AIH. The aim of our study is to determine the prevalence and the type of autoimmune disorders associated with AIH. Material and Methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for AIH. The diagnosis of AHI was based on the criteria of the revised International AIH group scoring system (IAIHG). Results: Twenty-for patients (21 women and 3 men) followed for AIH were collected. The mean age was 39 years (17-65 years). Among these patients, 11 patients(45.8%) had at least one autoimmune disease associated to AIH. These diseases were Hashimoto's thyroiditis (n = 5), Gougerot Sjogren syndrome (n=5), Primary biliary cirrhosis (n=2), Primitive sclerosant Cholangitis (n=1), Addison disease (n = 1) and systemic sclerosis (n=1). Patients were treated with corticosteroids alone or with azathioprine associated to the specific treatment of associated diseases with complete remission of AIH in 90% of cases and clinical improvement of other diseases. Conclusion: In our study, the prevalence of autoimmune diseases in AIH patients was 45.8%. These diseases were dominated by autoimmune thyroiditis and Gougerot Sjogren syndrome. The investigation of autoimmune diseases in autoimmune hepatitis must be systematic because of their frequency and the importance of adequate management.

Keywords: autoimmune diseases, autoimmune hepatitis, autoimmune thyroiditis, gougerot sjogren syndrome

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Authors: Prajna Metta, Yanti Rusyanti, Nunung Rusminah, Bremmy Laksono

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The decrease of neutrophil chemotaxis function may cause increased susceptibility to aggressive periodontitis (AP). Neutrophil chemotaxis is affected by formyl peptide receptor 1 (FPR1), which when activated will respond to bacterial chemotactic peptide formyl methionyl leusyl phenylalanine (FMLP). FPR1 protein value is decreased in response to a wide number of inflammatory stimuli in AP patients. This study was aimed to assess the alteration of FPR1 protein value in AP patients and if FPR1 protein value could be used as an indicator of neutrophil chemotaxis dysfunction in AP. This is a case control study with 20 AP patients and 20 control subjects. Three milliliters of peripheral blood were drawn and analyzed for FPR1 protein value with ELISA. The data were statistically analyzed with Mann-Whitney test (p>0,05). Results showed that the mean value of FPR1 protein value in AP group is 0,353 pg/mL (0,11 to 1,18 pg/mL) and the mean value of FPR1 protein value in control group is 0,296 pg/mL (0,05 to 0,88 pg/mL). P value 0,787 > 0,05 suggested that there is no significant difference of FPR1 protein value in both groups. The present study suggests that FPR1 protein value has no significance alteration in AP patients and could not be used as an indicator of neutrophil chemotaxis dysfunction.

Keywords: aggressive periodontitis, chemotaxis dysfunction, FPR1 protein value, neutrophil

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Authors: Li Yuchen, Wu Qingxin, Jin Yuxing, Yang Qian

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Interleukin-11 (IL-11), a well-known anti-inflammatory factor, helps to protect against intestinal epithelium damage caused by physical or chemical factors. However, little is known about the role of IL-11 during viral infection. Herein, high mRNA and protein levels of IL-11 were found in epithelial cells and jejunum of piglets during porcine epidemic diarrhea virus (PEDV) infection, and IL-11 expression was positively correlated with the level of viral infection. Pretreatment with recombinant porcine IL-11 (pIL-11) suppressed PEDV replication in Vero E6 cells, while IL-11 knockdown promoted viral infection. Furthermore, pIL-11 inhibited viral infection by preventing PEDV-mediated apoptosis of cells through activating the IL-11/STAT3 signal pathway. Conversely, application of a STAT3 phosphorylation inhibitor significantly antagonized the anti-apoptosis function of pIL-11 and counteracted its inhibition of PEDV. Our data suggested that that IL-11 is a novel PEDV-inducible cytokine, and its production enhances the anti-apoptosis ability of epithelial cells against PEDV infection. The potential uses of IL-11 as a novel therapeutic against devastating viral diarrhea in piglets deserves more attention and study.

Keywords: Interleukin-11, Porcine epidemic diarrhea virus, STAT3, anti-apoptosis

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Authors: Mohsen Salesi, Seyyed Zoheir Rabei

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Exercise has been considered a cornerstone of diabetes prevention and treatment for decades, but the benefits of resistance training are less clear. The purpose of this study was to determine the impact of resistance training on blood profile and inflammatory marker (CRP) of type 2 diabetes mellitus people. Thirty diabetic male were recruited (age: 50.34±10.28 years) and randomly assigned to 8 weeks resistance exercise training (n=15) and control groups (n=15). Before and after training blood pressure, weight, lipid profile (TC, TG, LDL-c, and HDL-c) and hs-CRP were measured. The resistance exercise training group took part in supervised 50–80 minutes resistance training sessions, three days a week on non-consecutive days for 8 weeks. Each exercise session included approximately 10 min of warm-up and cool-down periods. Results showed that TG significantly decreased (pre 210.19±9.31 vs. 101.12±7.25, p=0.03) and HDL-c significantly increased (pre 42.37±3.15 vs. 47.50±2.19, p=0.01) after exercise training. However, there was no difference between groups in TC, LDL-c, BMI and weight. In addition, a decrease in fasting blood glucose levels showed significant difference between groups (pre 144.65±5.73 vs. 124.21±6.48 p=0.04). Regular resistance exercise training can improve the lipid profile and reducing the cardiovascular risk factors in T2DM patients.

Keywords: lipid profile, resistance exercise, type 2 diabetes mellitus, men

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Authors: Austin Belfiori, Kevin Rinek, Zach Barcroft, Jennifer Berglind

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Diet influences the composition of the gut microbiota and host's health. Disruption of the balance among the microbiota, epithelial cells, and resident immune cells in the intestine is involved in the pathogenesis of inflammatory bowel disease (IBD). To study the role of gut microbiota in intestinal inflammation, the microbiome of control mice (C57BL6) given a gluten-containing standard diet versus C57BL6 mice given the gluten-free (GF) feed (n=10 in each group) was examined. All mice received the 3% DSS for 5 days. Throughout the study, feces were collected and processed for DNA extraction and MiSeq Illumina sequencing of V4 region of bacterial 16S rRNA gene. Alpha and beta diversities and compositional differences at phylum and genus levels were determined in intestinal microbiota. The mice receiving the GF diet showed a significantly increased abundance of Firmicutes and a decrease of Bacteroides and Lactobacillus at phylum level. Therefore, the gluten free diet led to reductions in beneficial gut bacteria populations. These findings indicate a role of wheat gluten in dysbiosis of the intestinal microbiota.

Keywords: gluten, colitis, microbiota, DSS, dextran sulphate sodium

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Authors: Sunil Kamboj, Vipin Saini, Suman Bala, Gaurav Sharma

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The main aim of the present research was to encapsulate mefenamic acid in niosomes and incorporate the prepared niosomes in the carbopol gel base for sustained therapeutic action. Mefenamic acid loaded niosomes were prepared by thin film hydration technique and evaluated for entrapment efficiency, vesicular size and zeta potential. The entrapment efficiency of the prepared niosomes was found to increase with decreasing the HLB values of surfactants and vesicle size was found to increase with increasing the cholesterol concentration. Niosomal vesicles with good entrapment efficiencies were incorporated in carbopol gel base to form the niosomal gel. The prepared niosomal gel was evaluated for pH, viscosity, spreadability, extrudability and skin permeation study across the rat skin.The results of permeation study revealed that the gel formulated with span 60 niosomes sustained the drug release for 12 h. Further the in vivo study showed the good inhibition of inflammation by the gel prepared with span 60 niosomes.

Keywords: mefenamic acid, niosomal gel, nonionic surfactants, sustained release

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Authors: Kiran Datta, Daniella Holland-Hart, Anthony Byrne

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Introduction: Oesophago-gastric (OG) cancers are the fifth commonest in the UK, accounting for over 12,000 deaths each year. Most patients will present at later stages of the disease, with only 21% of patients with stage 4 disease surviving longer than a year. As a result, many patients are unsuitable for curative surgery and instead receive palliative treatment to improve prognosis and symptom burden. However, palliative chemotherapy can result in significant toxicity: almost half of the patients are unable to complete their chemotherapy regimen, with this proportion rising significantly in older and frailer patients. In addition, clinical trials often exclude older and frailer patients due to strict inclusion criteria, meaning there is limited evidence to guide which patients are most likely to benefit from palliative chemotherapy. Inappropriate chemotherapy administration is at odds with the goals of palliative treatment and care, which are to improve quality of life, and this also represents a significant resource expenditure. This literature review aimed to examine and appraise evidence regarding treatment resilience in order to guide clinicians in identifying the most suitable candidates for palliative chemotherapy. Factors influencing treatment resilience were assessed, as measured by completion rates, dose reductions, and toxicities. Methods: This literature review was conducted using rapid review methodology, utilising modified systematic methods. A literature search was performed across the MEDLINE, EMBASE, and Cochrane Library databases, with results limited to papers within the last 15 years and available in English. Key inclusion criteria included: 1) participants with either oesophageal, gastro-oesophageal junction, or gastric cancers; 2) patients treated with palliative chemotherapy; 3) available data evaluating the association between baseline participant characteristics and treatment resilience. Results: Of the 2326 papers returned, 11 reports of 10 studies were included in this review after excluding duplicates and irrelevant papers. Treatment resilience factors that were assessed included: age, performance status, frailty, inflammatory markers, and sarcopenia. Age was generally a poor predictor for how well patients would tolerate chemotherapy, while poor performance status was a better indicator of the need for dose reduction and treatment non-completion. Frailty was assessed across one cohort using multiple screening tools and was an effective marker of the risk of toxicity and the requirement for dose reduction. Inflammatory markers included lymphopenia and the Glasgow Prognostic Score, which assessed inflammation and hypoalbuminaemia. Although quick to obtain and interpret, these findings appeared less reliable due to the inclusion of patients treated with palliative radiotherapy. Sarcopenia and body composition were often associated with chemotherapy toxicity but not the rate of regimen completion. Conclusion: This review demonstrates that there are numerous measures that can estimate the ability of patients with oesophago-gastric cancer to tolerate palliative chemotherapy, and these should be incorporated into clinical assessments to promote personalised decision-making around treatment. Age should not be a barrier to receiving chemotherapy and older and frailer patients should be included in future clinical trials to better represent typical patients with oesophago-gastric cancers. Decisions regarding palliative treatment should be guided by these factors identified as well as patient preference.

Keywords: frailty, oesophago-gastric cancer, palliative chemotherapy, treatment resilience

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Authors: Ammara Khan

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Sepsis is characterized by an overwhelming surge of cytokines and oxidative stress to one of many factors, gram-negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damages including hepatotoxicity.The present study was aimed to ascertain the adequacy of three different drugs delivered separately and collectively- low dose steroid-dexamethasone (3mg/kg i.p) ,antioxidant-melatonin(10 mg/kg i.p) ,and phosphodiesterases inhibitor - pentoxifylline (75 mg/kg i.p)in endotoxin-induced hepatotoxicity in mice. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E.Coli intraperitoneally. The preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas the therapeutic potential of the experimental agent was searched out via post-LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with a histopathological examination of liver tissue. Dexamethasone is given before (Group 3) and after LPS (group 4) significantly attenuated LPS generated liver injury.Pentoxifylline generated similar results and serum ALT; AST histological alteration abated considerably (p≤ 0.05) both in animals subjected to pentoxifylline pre (Group 5) and post-treatment(Group 6). Melatonin was also prosperous in aversion (Group 7) and curation (Group 8) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes in liver sections (p≤0.05). Combination therapies with dexamethasone in conjunction with melatonin (Group 9), dexamethasone together with pentoxifylline (Group 10), and pentoxifylline along with melatonin (Group 11) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably. In conclusion, both melatonin and pentoxifylline set up promising results in endotoxin-induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis-induced liver failure.

Keywords: endotoxin/lipopolysacchride, dexamethasone, hepatotoxicity, melatonin, pentoxifylline

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Authors: Laura Bellassen, Idit Shachar

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Multiple sclerosis (MS) is a chronic neurological disorder characterized by demyelination of the central nervous system (CNS), leading to a wide range of physical and cognitive impairments. Myeloid cells in the CNS, such microglia and border associated macrophage cells, participate in the neuroinflammation in MS. Activation of those cells in MS contributes to the inflammatory response in the CNS and recruitment of immune cells in the this compartment. SLAMF5 is a cell surface receptor that functions as a homophilic adhesion molecule, whose signaling can activate or inhibit leukocyte function. In the current study we followed the expression and function of SLAMF5 in myeloid cells in the CNS and in the periphery in the murine model for MS, the experimental autoimmune encephalomyelitis model (EAE). Our results show that SLAMF5 deficiency or blocking decreases the expression of activation molecules and costimulatory molecules such as MHCII and CD80, resulting in delayed onset and reduced progression of the disease. Moreover, blocking SLAMF5 in peripheral monocytes derived from MS patients and iPSC-derived microglia cells, controls the expression of HLA-DR and CD80. Thus, SLAMF5 is a regulator of myeloid cells function and can serve as a therapeutic target in autoimmune disorders as Multiple Sclerosis.

Keywords: multiple sclerosis, EAE model, myeloid cells, new antibody, neuroimmunology

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Authors: Farzaneh Ziaee, Mohammad Ziaee

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N-acetyl-L-cysteine (NAC) is a well-known mucolytic agent, and recently its efficacy has been examined for the prevention and remediation of several diseases such as lung infections caused by Coronavirus. Also, it is administrated as the main antidote in paracetamol overdose and is effective for the treatment of idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD). This medicine is used as an antioxidant to prevent diabetic kidney disease (nephropathy). In this study, a method for the acylation of amino acids is employed to manufacture this drug in a height yield. Regarding this patented path, NAC can be made in a single batch step at ambient pressure and temperature. Moreover, this study offers a technique to make peptide bonds which is of interest for pharmaceutical and medicinal industries. The separation process was undertaken using appropriate solvents to achieve an excellent purification level. The synthesized drug was characterized via proton nuclear magnetic resonance (1H NMR), high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FT-IR), elemental analysis, and melting point.

Keywords: N-acetylcysteine, synthesis, mucolytic medication, lung anti-inflammatory, COVID-19, antioxidant, pharmaceutical supplement, characterization

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Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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Authors: D. Baranova, E. Neborak

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Polyphenols, particularly flavonoids like quercetin, fisetin, and kaempferol, have gained significant attention in nutrition due to their antioxidant, senolytic, and anti-inflammatory properties. These compounds are commonly found in various plant-based foods and are represented by diverse subclasses, each with unique health benefits. Understanding their absorption, metabolism, and bioactivity within the human body is crucial for unlocking their full potential. Quercetin, for instance, exists in multiple forms, impacting its solubility and absorption in the intestine. Its intake, often derived from sources like apples, is affected by cooking methods, with medium heat retaining its potency. Fisetin, also present in fruits and vegetables, demonstrates neuroprotective qualities and stability under varied conditions compared to quercetin. Similarly, kaempferol, found in fruits and vegetables, displays antioxidative effects but is influenced by cooking techniques, with specific methods preserving its polyphenolic content better. Overall, these polyphenols offer promising health benefits, yet their optimal dosage and specific dietary recommendations warrant further research to harness their full nutritional potential.

Keywords: polyphenols, flavonoids, absorption, quercetin, kaempferol, fisetin, senolytics, absorption, cooking method

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Authors: Nneka Nkechi Uchegbu, Temitope Omolayo Fasuan

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This study investigated how to reduce bio-compounds and amino acids in V. amygdalina leaf during processing as a functional food ingredient. Fresh V. amygdalina leaf was processed using thermal oil-aqueous mixtures (soybean oil: aqueous and palm oil: aqueous) at 1:40 and 130 (v/v), respectively. Results indicated that the hot soybean oil-aqueous mixture was the most effective in preserving the bio-compounds and amino acids with retention potentials of 80.95% of the bio-compounds at the rate of 90-100%. Hot palm oil-aqueous mixture retained 61.90% of the bio-compounds at the rate of 90-100% and hot aqueous retained 9.52% of the bio-compounds at the same rate. During the debittering process, seven new bio-compounds were formed in the leaves treated with hot soybean oil-aqueous mixture, six in palm oil-aqueous mixture, and only four in hot aqueous leaves. The bio-compounds in the treated leaves have potential functions as antitumor, antioxidants, antihistaminic, anti-ovarian cancer, anti-inflammatory, antiarthritic, hepatoprotective, antihistaminic, haemolytic 5-α reductase inhibitor, nt, immune-stimulant, diuretic, antiandrogenic, and anaemiagenic. Alkaloids and polyphenols were retained at the rate of 81.34-98.50% using oil: aqueous mixture while aqueous recorded the rate of 33.47-41.46%. Most of the essential amino acids were retained at a rate above 90% through the aid of oil. The process is scalable and could be employed for domestic and industrial applications.

Keywords: V. amygdalina leaf, bio-compounds, oil-aqueous mixture, amino acids

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Authors: Mahdi Asghari Ozma

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Background and Objective:Maclurapomifera (Rafin.) Schneider, known as osage orange, is a north american native plant which has multiple applications in herbal medicine. The extract of this plant has many therapeutic effects, including antimicrobial, anti-tumor, anti-inflammation, etc., that discussed in this study. Materials and Methods: For this study, the keywords "Maclurapomifera", "osage orange, ""herbal medicine ", and "plant extract" in the databases PubMed and Google Scholar between 2002 and 2021 were searched, and 20 articles were chosen, studied and analyzed. Results: Due to the increased resistance of microbes to antibiotics, the need for antimicrobial plants is increasing. Maclurapomifera is one of the plants with antimicrobial properties that can affect all microbes, especially Gram-negative bacteria, and fungi. This plant also has anti-tumor, anti-inflammatory, anti-oxidant, anti-aging, antiviral, anti-fungal, anti-ulcerogenic, anti-diabetic, and anti-nociceptive effects, which can be used as a substance with many amazing therapeutic applications. Conclusion: These results suggest that the extract of Maclurapomifera can be used in clinical medicine as a remedial agent, which can be substituted for chemical drugs or help them in the treatment of diseases.

Keywords: maclura pomifera, osage orange, herbal medicine, plant extract

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Authors: Elif Yildiz, Gizem Gungor, Hatice Yilmaz, Duygu Gocmen

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Nowadays, consumer demand has been increasing for the healthy and functional food. In this context, some natural products rich in phenolic compounds are also added to cereal based food for health benefits. Natural phenolic compounds have many beneficial bioactivities such as anti-allergic, antiviral, anti-inflammatory and anti-mutagenic activities. It has been found that various plant species contain natural bioactive phytochemicals with antioxidant function. One of these plant species is mahaleb (Prunus mahaleb L). Mahaleb berries with dark blue or red colours have the highest antioxidant capacities among all common fruits and vegetables. The aim of this study was to determine the possibilities of improving the antioxidant properties of novel snack crackers by supplementing with mahaleb (Prunus mahaleb L) powder. For this purpose mahaleb powder were used to replace wheat flour in the snack cracker formulation at two different levels (5%, and 7.5% w/w). As a result, mahaleb supplementation caused an increase in total phenolic contents and antioxidant activities of crackers. It can be say that mahaleb powder can be used as an alternative functional and nutritional ingredient in bakery products.

Keywords: antioxidant activity, cracker, mahaleb (Prunus mahaleb L), phenolic contents

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Authors: Zahia Aliche, Fatiha Boudjema, Benyoucef Khelidj, Selma Mettai, Zohra Bouriahi, Saliha Mohammed Belkebir, Ridha Mazouz

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The purpose of this work is the study of the viscoelastic behaviour formulating gels based plant extractions. The extracts of Zingibar officinale and Cinnamomum cassia were included in the gel at different concentrations of these plants in order to be applied in anti-inflammatory drugs. The yield of ethanolic extraction of Zingibar o. is 3.98% and for Cinnamomum c., essential oil by hydrodistillation is 1.67 %. The ethanolic extract of Zingibar.o, the essential oil of Cinnamomum c. and the mixture showed an anti-DPPH radicals’ activity, presented by EC50 values of 11.32, 13.48 and 14.39 mg/ml respectively. A gel based on different concentrations of these extracts was prepared. Microbiological tests conducted against Staphylococcus aureus and Escherichia colishowed moderate inhibition of Cinnamomum c. gel and less the gel based on Cinnamomum c./ Zingibar o. (20/80). The yeast Candida albicansis resistant to gels. The viscoelastic formulation property was carried out in dynamic and creep and modeled with the Kelvin-Voigt model. The influence of some parameters on the stability of the gel (time, temperature and applied stress) has been studied.

Keywords: Cinnamomum cassia, Zingibar officinale, antioxidant activity, antimicrobien activity, gel, viscoelastic behaviour

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Authors: U. L. Fulco, E. L. Albuquerque, José X. Lima Neto, L. R. Da Silva

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The binding of the nonsteroidal anti-inflammatory drug ibuprofen (IBU) to human serum albumin (HSA) is investigated using density functional theory (DFT) calculations within a fragmentation strategy. Crystallographic data for the IBU–HSA supramolecular complex shows that the ligand is confined to a large cavity at the subdomain IIIA and at the interface between the subdomains IIA and IIB, whose binding sites are FA3/FA4 and FA6, respectively. The interaction energy between the IBU molecule and each amino acid residue of these HSA binding pockets was calculated using the Molecular Fractionation with Conjugate Caps (MFCC) approach employing a dispersion corrected exchange–correlation functional. Our investigation shows that the total interaction energy of IBU bound to HSA at binding sites of the fatty acids FA3/FA4 (FA6) converges only for a pocket radius of at least 8.5 °A, mainly due to the action of residues Arg410, Lys414 and Ser489 (Lys351, Ser480 and Leu481) and residues in nonhydrophobic domains, namely Ile388, Phe395, Phe403, Leu407, Leu430, Val433, and Leu453 (Phe206, Ala210, Ala213, and Leu327), which is unusual. Our simulations are valuable for a better understanding of the binding mechanism of IBU to albumin and can lead to the rational design and the development of novel IBU-derived drugs with improved potency.

Keywords: ibuprofen, human serum albumin, density functional theory, binding energies

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Authors: Justina I. R. Udotong, Ofonime U. M. John

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Toxicity of copper (Cu), lead (Pb) and iron (Fe) to Tilapia guinensis was carried out for 4 days with a view to determining their effects on the liver and muscle tissues. Tilapia guinensis samples of about 10 - 14cm length and 0.2 – 0.4kg weight each were obtained from University of Calabar fish ponds and acclimated for three (3) days before the experimental set up. Survivors after the 96-hr LC50 test period were selected from test solutions of the heavy metals for the histopathological studies. Histological preparations of liver and muscle tissues were randomly examined for histopathological lesions. Results of the histological examinations showed gross abnormalities in the liver tissues due to pathological and degenerative changes compared to liver and muscle tissues from control samples (tilapia fishes from aquaria without heavy metals). Extensive hepatocyte necrosis with chronic inflammatory changes was observed in the liver of fishes exposed to Cu solution. Similar but less damaging effects were observed in the liver of fishes exposed to Pb and Fe. The extent of lesion observed was therefore heavy metal-related. However, no pathologic changes occurred in the muscle tissues.

Keywords: degenerative changes, heavy metal, hepatocyte necrosis, histopathology, toxicity

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Authors: Ali Baker, Russel Krawitz

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This paper describes a rare occurrence where a potentially fatal complication of COVID-19 infection (MIS-A) was misdiagnosed as an acute abdomen. As most patients with this syndrome present with fever and gastrointestinal symptoms, they may inadvertently fall under the care of the surgical unit. However, unusual imaging findings and a poor response to anti-microbial therapy should prompt clinicians to suspect a non-surgical etiology. More than half of MIS-A patients require ICU admission and vasopressor support. Prompt referral to a physician is key, as the cornerstone of treatment is IVIG and corticosteroid therapy. A 32 year old woman presented with right sided abdominal pain and fevers. She had also contracted COVID-19 two months earlier. Abdominal examination revealed generalised right sided tenderness. The patient had raised inflammatory markers, but other blood tests were unremarkable. CT scan revealed extensive lymphadenopathy along the ileocolic chain. The patient proved to be a diagnostic dilemma. She was reviewed by several surgical consultants and discussed with several inpatient teams. Although IV antibiotics were commenced, the right sided abdominal pain, and fevers persisted. Pan-culture returned negative. A mild cholestatic derangement developed. On day 5, the patient underwent preparation for colonoscopy to assess for a potential intraluminal etiology. The following day, the patient developed sinus tachycardia and hypotension that was refractory to fluid resuscitation. That patient was transferred to ICU and required vasopressor support. Repeat CT showed peri-portal edema and a thickened gallbladder wall. On re-examination, the patient was Murphy’s sign positive. Biliary ultrasound was equivocal for cholecystitis. The patient was planned for diagnostic laparoscopy. The following morning, a marked rise in cardiac troponin was discovered, and a follow-up echocardiogram revealed moderate to severe global systolic dysfunction. The impression was post-COVID MIS with myocardial involvement. IVIG and Methylprednisolone infusions were commenced. The patient had a great response. Vasopressor support was weaned, and the patient was discharged from ICU. The patient continued to improve clinically with oral prednisolone, and was discharged on day 17. Although MIS following COVID-19 infection is well-described syndrome in children, only recently has it come to light that it can occur in adults. The exact incidence is unknown, but it is thought to be rare. A recent systematic review found only 221 cases of MIS-A, which could be included for analysis. Symptoms vary, but the most frequent include fever, gastrointestinal, and mucocutaneous. Many patients progress to multi-organ failure and require vasopressor support. 7% succumb to the illness. The pathophysiology of MIS is only partly understood. It shares similarities with Kawasaki disease, macrophage activation syndrome, and cytokine release syndrome. Importantly, by definition, the patient must have an absence of severe respiratory symptoms. It is thought to be due to a dysregulated immune response to the virus. Potential mechanisms include reduced levels of neutralising antibodies and autoreactive antibodies that promote inflammation. Further research into MIS-A is needed. Although rare, this potentially fatal syndrome should be considered in the unwell surgical patient who has recently contracted COVID-19 and poses a diagnostic dilemma.

Keywords: acute-abdomen, MIS, COVID-19, ICU

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Authors: Kuei-Ling Sun, Emily Chia-Yu Su

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Allergy is a hypersensitive overreaction of the immune system to environmental stimuli, and a major health problem. These overreactions include rashes, sneezing, fever, food allergies, anaphylaxis, asthmatic, shock, or other abnormal conditions. Allergies can be caused by food, insect stings, pollen, animal wool, and other allergens. Their development of allergies is due to both genetic and environmental factors. Allergies involve immunoglobulin E antibodies, a part of the body’s immune system. Immunoglobulin E antibodies will bind to an allergen and then transfer to a receptor on mast cells or basophils triggering the release of inflammatory chemicals such as histamine. Based on the increasingly serious problem of environmental change, changes in lifestyle, air pollution problem, and other factors, in this study, we both collect allergens and non-allergens from several databases and use several machine learning methods for classification, including logistic regression (LR), stepwise regression, decision tree (DT) and neural networks (NN) to do the model comparison and determine the permutations of allergen amino acid’s sequence.

Keywords: allergy, classification, decision tree, logistic regression, machine learning

Procedia PDF Downloads 278

Authors: Xingxin Wu, Fenli Shao, Tao Tan, Yang Tan, Yang Sun, Qiang Xu

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Psoriasis is a chronic inflammatory skin disease that affects about 2% of the world's population. IL-23 signaling plays a key role in the pathogenesis of psoriasis. Control of IL-23 release by small molecule compounds during developing psoriasis has not been well established. Here, we show that compound 1, a small molecule nature product, protected mice from imiquimod-induced psoriasis with improved skin lesions, reduced skin thickness, and reduced IL-23 mRNA expression in the skin tissue. FACS results showed compound 1 reduced the number of dendritic cells in the skin. Interestingly, compound 1 was not able to ameliorate IL-23-induced psoriasis-like skin inflammation in mice. Further, compound 1 inhibited MyD88-dependent IL-23 mRNA expression induced by LPS, CpG and imiquimod in BMDC cells, but not MyD88-independent CD80 and CD86 expression induced by LPS. The methods included real-time PCR, western blot, H & E staining, FACS and ELISA et al. In conclusion, compound 1 regulates MyD88-dependent signaling to control IL-23 release in dendritic cells, which improves imiquimod-induced psoriasis.

Keywords: dendritic cells, IL-23, toll-like receptor signaling, psoriasis

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Authors: Chiara Colarusso, Michela Terlizzi, Aldo Pinto, Rosalinda Sorrentino

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Cigarette smoking is the main cause and the most common risk factor for both COPD and lung cancer. In our previous studies, we proved that caspase-11 in mice and its human analogue, caspase-4, are involved in lung carcinogenesis and that AIM2 inflammasome might play a pro-cancerous role in lung cancer. Therefore, the aim of this study was to investigate potential crosstalk between COPD and lung cancer, focusing on AIM2 and caspase-11-dependent inflammasome signaling pathway. To mimic COPD, we took advantage of an experimental first-hand smoking mouse model and, to confirm what was observed in mice, we used human samples of lung adenocarcinoma patients stratified according to the smoking and COPD status. We demonstrated that smoke exposure led to emphysema-like features, bronchial tone impairment, and release of IL-1-like cytokines (IL-1α, IL-1β, IL-33, IL-18) in a caspase-1 independent manner in C57Bl/6N. Rather, a dysfunctional caspase-11 in smoke-exposed 129Sv mice was associated to lower bronchial inflammation, collagen deposition, and IL-1-like inflammation. In addition, for the first time, we found that AIM2 inflammasome is involved in lung inflammation in smoking and COPD, in that its expression was higher in smoke-exposed C57Bl/6N compared to 129Sv smoking mice, who instead did not show any alteration of AIM2 in both macrophages and dendritic cells. Moreover, we found that AIM2 expression in the cancerous tissue, albeit higher than non-cancerous tissue, was not statistically different according to the COPD and smoking status. Instead, the higher expression of AIM2 in non-cancerous tissue of smoker COPD patients than smokers who did not have COPD was correlated to a higher hazard ratio of poor survival rate than patients who presented lower levels of AIM2. In conclusion, our data highlight that caspase-11 in mice is associated to smoke-induced lung latent inflammation which could drive the establishment of lung cancer, and that AIM2 inflammasome plays a role at the crosstalk between smoking/COPD and lung adenocarcinoma in that its higher presence is correlated to lower survival rate of smoker COPD adenocarcinoma.

Keywords: COPD, inflammasome, lung cancer, lung inflammation, smoke

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Authors: Manea A. I. Alqrad, Alaa Sirwi, Sabrin R. M. Ibrahim, Hossam M. Abdallah, Gamal A. Mohamed

Abstract:

Phytochemical study of the methanolic extract of the air dried powdered of the parts of Viscum schemperi Engl. (Family: Viscaceae) using different chromatographic techniques led to the isolation of five compounds: -amyrenone (1), betulinic acid (2), (3β)-olean-12-ene-3,23-diol (3), -oleanolic acid (4), and α-oleanolic acid (5). Their structures were established based on physical, chemical, and spectral data. Anti-inflammatory and anti-apoptotic activities of oleanolic acid in a mouse model of acute hepatorenal damage were assessed. This study showed the efficacy of oleanolic acid to counteract thioacetamide-induced hepatic and kidney injury in mice through the reduction of hepatocyte oxidative damage, suppression of inflammation, and apoptosis. More importantly, oleanolic acid suppressed thioacetamide-induced hepatic and kidney injury by inhibiting NF-κB/TNF-α-mediated inflammation/apoptosis and enhancing SIRT1/Nrf2/Heme-oxygenase signalling pathway. These promising pharmacological activities suggest the potential use of oleanolic acid against hepatorenal damage.

Keywords: oleanolic acid, viscum schimperi, thioacetamide, SIRT1/Nrf2/NF-κB, hepatorenal damage

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Authors: Abdelkrim Cheriti, Mebarka Belboukhari, Nasser Belboukhari

Abstract:

Launaea Cass. is a small genus of the family Asteraceae (tribe Lactuceae, subtribe Sonchinae), consisting of 54 species, of which 9 are presented in the flora of Algeria and is mainly distributed in the South Mediterranean, Africa and SW Asia. Plants in the Launaea genus have been used ethnobotanically as bitter stomachic, for treating diarrhea, gastrointestinal tracts, as anti-inflammatory, for skin diseases, treatment of infected wounds, hepatic pains, children fever, as soporific, lactagogue, diuretic and as insecticidal. Antioxidants are vital substances, which possess the ability to protect the body from damages caused by free radical induced oxidative stress. A variety of free radical scavenging antioxidants is found in a number of dietary sources. The main objective of this study focused on the screening of antioxidant activity of Launaea nudicaulis (Asteraceae) extracts. The in vitro antioxidant activity was investigated with DPPH radical scavenging assay. The quantitative evaluation of DPPH scavenging activity showed that n-BuOH and EtOAc extracts are the most active extracts with a percentage of antiradical activity of 89,62% and 71,57% respectively.

Keywords: Launaea, phytochemical, South Algeria, Sahara, endemic specie

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Authors: Chieh-Nan Chen, Ji-Yu Lin, I-Ming Chu

Abstract:

Polypeptide thermosensitive hydrogel is an excellent candidate as a smart device to deliver drugs and cells due to its remarkable biocompatibility, low gelation concentration, and respond to temperature stimuli, it can be easily injected as a polymer solution into the patient’s body where it undergoes gelation due to an elevation in temperature. Poly (ethylene glycol) monomethyl ether-poly (ethyl-l-glutamate) (mPEG-PELG) contains a hydrophobic side chain –C2H5 which is useful in encapsulating and stabilizing hydrophobic drugs. In this study, we plan to focus on the hydrophobic anti-carcinogenic and anti-inflammatory drug curcumin, which due its insolubility in water, requires a proper carrier for delivery into the body. Our main concept is to use mPEG-PELG to stabilize curcumin, inject the curcumin-loaded hydrogel into the tumor site, and allow the enzymatically-sensitive hydrogel to be degraded by bodily fluids and release the drug. The polymers of interest have been successfully synthesized and characterized by 1H-NMR, FT-IR, SEM, and CMC. Curcumin loading content and drug release were assayed using HPLC. Preliminary results show that these materials have potential as a delivery vehicle for poorly soluble drugs.

Keywords: curcumin, drug release, hydrogel, polypeptide material

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Authors: M. Yadegari, M. Nourbakhsh, N. Arbabzadeh

Abstract:

The skeletal system injuries are of major importance. In addition, it is recommended to use materials for hard tissue repair in open or closed fractures. It is important to use complex minerals with a beneficial effect on hard tissue repair, stimulating cell growth in the bone. Materials that could help avoid bone fracture inflammatory reaction and speed up bone fracture repair are of utmost importance in the treatment of bone fractures. Similar to minerals, the inner eggshell membrane consists of carbohydrates, lipids, proteins with the high pH, high calcium absorptive capacity and with faster bone fracture repair ability. In the present radiographic survey, eggshell-derived bone graft substitutes were used for bone defect repair in 8 dog tibia, measuring bone density on the day of implant placement and 30 and 60 days after placement. In fact, the result of this study shows the difference in bone growth and misshapen bones between treatment and control sites. Cell growth was adequate in treatment sites and misshapen bones were less frequent here than in control sites.

Keywords: bone repair, eggshell powder, implant, radiography

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Authors: Pear-Rarin Leelakunakorn, Patompong Satapornpong

Abstract:

Introduction: Dapsone is an anti-inflammatory and antibiotic drug that was widely used for the treatment of leprosy, acne fulminans, and dermatitis herpetiformis (DH). However, dapsone is the main cause that triggers severe cutaneous adverse reactions (SCARs), with a possibility of 0.4 to 3.6% of patients after initiating treatment. In fact, the mortality rate of dapsone-induced SCARs is approximately 9.9%. In previous studies, HLA-B*13:01 was strongly associated with dapsone-induced SCARs in Han Chinese, Thais, and Koreans. Nevertheless, the distribution of HLA-B*13:01 marker in each population might differ. Moreover, there were found that the association between HLA-C*03:04 and dapsone hypersensitivity syndrome in Han Chinese leprosy patients by OR = 9.00 and p-value = 2.23×10⁻¹⁹. Objective: The aim of this study was to investigate the distribution of HLA-C* 03:04 in Thailand's healthy population. Method: A total of 350 participants were HLA-C genotyping used sequence-specific oligonucleotides (PCR-SSOs). This study was approved by the Ethics Committee of Rangsit University Result : The most frequency of HLA -C alleles in Thais, consist of HLA -C* 01:02 (17.00 %), -C*08:01 (11.00%) , -C*07:02 (10.70%) , -C* 03:04 ( 9.10%) , -C* 03:02 (8.00%) , -C* 07:01 (6.30%), -C* 07:04 (4.60%), -C* 04:01 (4.40%) ,-C* 12:02 ( 4.30% ) ,and -C* 04:03(3.90%). Interestingly, HLA -C* 03:04 allele was similar to the distribution among Thais and other populations such as Eastern Europe (6.09%), Vietnam (7.42% ), East Croatia (2.25%), and Han Chinese (11.70%). Conclusion: Consequently, HLA-C*03:04 might serve as a pharmacogenetic marker for screening prior to initiation therapy with dapsone for prevention of dapsone-induced SCARs in Thai population.

Keywords: HLA-C*03:04, SCARs, thai population, allele frequency

Procedia PDF Downloads 102

Authors: Jyh-Cheng Chen, Tai-Jing Wang, Yun-Wei Lin

Abstract:

Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Treatment with astaxanthin decreased Rad51 expression and phospho-AKT protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector significantly rescued the decreased Rad51 protein and mRNA levels in astaxanthin-treated NSCLC cells. Combined treatment with PI3K inhibitors (LY294002 or wortmannin) and astaxanthin further decreased the Rad51 expression in NSCLC cells. Knockdown of Rad51 enhanced astaxanthin-induced cytotoxicity and growth inhibition in NSCLC cells. These findings may have implications for the rational design of future drug regimens incorporating astaxanthin for the treatment of NSCLC.

Keywords: astaxanthin, cytotoxicity, AKT, non-small cell lung cancer, PI3K

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Authors: Sirilak Kongkaew, Pathumwadee Yodmanee, Nopporn Kaiyawet, Arthitaya Meeprasert, Thanyada Rungrotmongkol, Toshikatsu Kaburaki, Hiroshi Noguchi, Fujio Takeuch, Nawee Kungwan, Supot Hannongbua

Abstract:

Behçet’s disease (BD) is a genetic autoimmune expressed by multisystemic inflammatory disorder mostly occurred at the skin, joints, gastrointestinal tract, and genitalia, including ocular, oral, genital, and central nervous systems. Most BD patients in Japan and Korea were strongly indicated by the genetic factor namely HLA-B*51 (especially, HLA-B*51:01) marker in HMC class I, while HLA-A*26:01 allele has been detected from the BD patients in Greek, Japan, and Taiwan. To understand the selective binding of the MICA-TM peptide towards the HLAs associated with BD, the molecular dynamics simulations were applied on the four HLA alleles (B*51:01, B*35:01, A*26:01, and A*11:01) in complex with such peptide. As a result, the key residues in the binding groove of HLA protein which play an important role in the MICA-TM peptide binding and stabilization were revealed. The Van der Waals force was found to be the main protein-protein interaction. Based on the binding free energy prediction by MM/PBSA method, the MICA-TM peptide interacted stronger to the HLA alleles associated to BD in the identical class by 7-12 kcal/mol. The obtained results from the present study could help to differentiate the HLA alleles and explain a source of Behçet’s disease.

Keywords: Behçet’s disease, MD simulations, HMC class I, autoimmune

Procedia PDF Downloads 375