Search results for: inflammatory%20cytokines

Authors: Shah Abbas

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Rheumatoid arthritis is a systemic, inflammatory autoimmune disease, affecting an overall 1% of the global population. Despite being tremendous efforts by scientists, early diagnosis of RA still has not been achieved. In the current study, a Graphene oxide (GO) based electrochemical sensor has been developed for early diagnosis of RA through Cyclic voltammetry. Chitosan (CHI), a CPnatural polymer has also been incorporated along with GO in order to enhance the biocompatibility and functionalization potential of the biosensor. CCPs are known antigens for Anti Citrullinated Peptide Antibodies (ACPAs) which can be detected in serum even 14 years before the appearance of symptoms, thus they are believed to be an ideal target for the early diagnosis of RA. This study has yielded some promising results regarding the binding and detection of ACPAs through changes in the electrochemical properties of biosensing material. The cyclic voltammogram of this biosensor reflects the binding of ACPAs to the biosensor surface, due to its shifts observed in the current flow (cathodic current) as compared to the when no ACPAs bind as it is absent in RA negative patients.

Keywords: rheumatoid arthritis, peptide sensor, graphene oxide, anti citrullinated peptide antibodies, cyclic voltammetry

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Authors: Huamin Xu, Wenting Jia, Hong Jiang, Junxia Xie

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Rosmarinic acid (RA) is a natural acid that is found in a variety of herbs, such as rosemary and has multiple biological activities such as antioxidative, anti-inflammatory and antiviral activities. In this study, we investigated the neuroprotective effects of RA on dopaminergic system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model of Parkinson’s disease (PD). The mice received oral administration of RA before MPTP injection. Results showed that the tyrosine hydroxylase expression in SN reduced and the levels of dopamine and its metabolites in the striatum decreased in MPTP intoxicated PD mice. Pretreatment with RA significantly inhibited these changes. Further studies demonstrated that MPTP treatment increased the iron content, which was counteracted by pre-treatment with RA. In addition, RA could restore the decrease of superoxide dismutase (SOD) induced by MPTP. This study provides evidence that RA could suppress MPTP-induced degeneration of the nigrostriatal dopaminergic system by regulating iron content and the expression of SOD. Thus, RA might be clinically evaluated for the prevention of neurodegenerative diseases.

Keywords: rosmarinic acid, Parkinson's disease, MPTP, dopaminergic system

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Authors: M. M. Bashandy, A. R. Ahmed, M. El-Gaffary, Sahar S. Abd El-Rahman

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This study evaluated the acute toxicity and tissue distribution of intravenously administered gold nanoparticles (AuNPs) in male rabbits. Rabbits were exposed to single dose of AuNPs (300 µg/ kg). Toxic effects were assessed via general behavior, hematological parameters, serum biochemical parameters and histopathological examination of various rabbits’ organs. Tissue distribution of AuNPs was evaluated at a dose of 300 µg/ kg in male rabbit. Inductively coupled plasma–mass spectrometry (ICP-MS) was used to determine gold concentrations in tissue samples collected at predetermined time intervals. After one week, AuNPs exerted no obvious acute toxicity in rabbits. However, inflammatory reactions in lung and liver cells were induced in rabbits treated at the300 µg/ kg dose level. The highest gold levels were found in the spleen, followed by liver, lungs and kidneys. These results indicated that AuNPs could be distributed extensively to various tissues in the body, but primarily in the spleen and liver.

Keywords: gold nanoparticles, toxicity, pathology, hematology, liver function, kidney function

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Authors: Elham Rezaee, Sayyed Abbas Tabatabai

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Dual inhibition of COX-2 and sEH enzymes represents one of the distinct pharmaceutical approaches for the treatment of inflammation, pain, cancers, and other diseases. The discovery of these inhibitors for treatment is a great deal of attention because of some advantages such as increased efficacy, a promising safety profile, ease of formulation, and better target engagement. In this research, based on the structure-activity relationship of COX-2 and sEH inhibitors, some amide derivatives with oxadiazole and dihydropyrimidinone rings against sEH and COX-2 enzymes were developed. The designed compounds showed high affinity to the active site of both enzymes in docking studies and were synthesized in good yield and characterized by IR, Mass, 1HNMR, and 13CNMR. All of the novel compounds exhibited considerable in-vitro sEH and COX-2 inhibitory activities in comparison with 12-(3-Adamantan-1-yl-ureido)- dodecanoic acid and celecoxib (a potent urea-based sEH inhibitor and selective nonsteroidal anti-inflammatory drug, respectively). Ethyl 6-methyl-4-(4-(4-(methylsulfonyl)benzamido)phenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate was found to be the most selective COX-2 inhibitor (COX-2/COX-1 ratio: 683) with IC50 value of 2.1 nM targeting sEH enzyme.

Keywords: COX-2, dual inhibitors, sEH, synthesis

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Authors: Alia Ragheb

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Philodendron species were reported in traditional medicine for the treatment of several diseases. From the 70% methanol extract of the aerial parts of Philodendron bipinnatifidum Schott ex Endl, nine flavonoid compounds were isolated and identified for the first time; saponarin, genkwanin 8-C-(2′′-O-β-glucopyranosyl)-β-glucopyranoside, apigenin 6-C-(2′′-O-β-glucopyranosyl)-β-glucopyranoside, schaftoside, swertisin, swertiajaponin, isoswertisin, isorhamnetin 3-O-(2′′-acetyl)-β-glucopyranoside and apigenin. Characterization of the plant was achieved using chromatographic, physical, chemical, spectroscopic, and spectrometric techniques. The 70% methanol aerial parts extract and the methanol fraction of the plant were in vivo screened for their acute anti-inflammatory, antipyretic and analgesic effects where significant effects were exhibited compared to that of reference drugs. From the reported literature, these biological activities could be attributed to its phenolic constituent. The 70% methanol aerial parts and successive extracts, as well as some pure isolated flavonoid compounds, were in vitro investigated for their antioxidant, antimicrobial and cytotoxic activities.

Keywords: antioxidant, araceae, cytotoxicity, flavonoids

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Authors: Samiah Rehman, Kashmira J. Gohil

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Objective: Dracaena trifascaita extract (DTE) possesses strong antioxidant and anti-inflammatory properties that play a vital role in the treatment of mental disorders like depression. The present study was designed to evaluate the antidepressant effects of hydroalcoholic extracts of DT on behavioral models of depression. Methodology: Animals were randomly divided into 6 groups of 5 each: Group 1 and 2 received distilled water and standard drug, imipramine: 25mg/kg, respectively. Groups 4, 5 and 6 received DTE treatment orally at doses of 200 ,400 and 600mg/ kg, respectively, for 14 days. Time of immobility was noted by force swimming test (FST)and tail suspension test (TST) on the 1st,7th and 14th days. Results: The time of immobility was reduced in the treatment group as compared to the control and standard. DTE600 mg/kg showed the highest and most significant antidepressant effects as compared to the standard drug imipramine. (25mg/kg). Conclusion: DTE has good potential as an alternative therapy for depression.

Keywords: Dracaena trifasciata, antidepressants, force swimming test, tail suspension test, herbal drug of depression

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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: Jyh-Ping Chen, Yu-Tin Lai

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Wound healing is a complicated process involving overlapping hemostasis, inflammation, proliferation, and maturation phases. Ideal wound dressings can replace native skin functions in full thickness skin wounds through faster healing rate and also by reducing scar formation. Poly(lactic-co-glycolic acid) (PLGA) is an U.S. FDA approved biodegradable polymer to be used as ideal wound dressing material. Several in vitro and in vivo studies have demonstrated the effectiveness of curcumin in decreasing the release of inflammatory cytokines, inhibiting enzymes associated with inflammations, and scavenging free radicals that are the major cause of inflammation during wound healing. Heparin has binding affinities to various growth factors. With the unique and beneficial features offered by those molecules toward the complex process of wound healing, we postulate a composite wound dressing constructed from PLGA, curcumin and heparin would be a good candidate to accelerate scarless wound healing. In this work, we use electrospinning to prepare curcumin-loaded aligned PLGA nanofibrous membranes (PC NFMs). PC NFMs were further subject to oxygen plasma modification and surfaced-grafted with heparin through carbodiimide-mediated covalent bond formation to prepare curcumin-loaded PLGA-g-heparin (PCH) NFMs. The nanofibrous membranes could act as three-dimensional scaffolds to attract fibroblast migration, reduce inflammation, and increase wound-healing related growth factors concentrations at wound sites. From scanning electron microscopy analysis, the nanofibers in each NFM are with diameters ranging from 456 to 479 nm and with alignment angles within  0.5°. The NFMs show high tensile strength and good water absorptivity and provide suitable pore size for nutrients/wastes transport. Exposure of human dermal fibroblasts to the extraction medium of PC or PCH NFM showed significant protective effects against hydrogen peroxide than PLGA NFM. In vitro wound healing assays also showed that the extraction medium of PCH NFM showed significantly better migration ability toward fibroblasts than PC NFM, which is further better than PLGA NFM. The in vivo healing efficiency of the NFMs was further evaluated by a full thickness excisional wound healing diabetic rat model. After 14 days, PCH NFMs exhibits 86% wound closure rate, which is significantly different from other groups (79% for PC and 73% for PLGA NFM). Real-time PCR analysis indicated PC and PCH NFMs down regulated anti-oxidative enzymes like glutathione peroxidase (GPx) and superoxide dismutase (SOD), which are well-known transcription factors involved in cellular inflammatory responses to stimuli. From histology, the wound area treated with PCH NFMs showed more vascular lumen formation from immunohistochemistry of α-smooth muscle actin. The wound site also had more collagen type III (65.8%) expression and less collagen type I (3.5%) expression, indicating scar-less wound healing. From Western blot analysis, the PCH NFM showed good affinity toward growth factors from increased concentration of transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2) at the wound site to accelerate wound healing. From the results, we suggest PCH NFM as a promising candidate for wound dressing applications.

Keywords: Curcumin, heparin, nanofibrous membrane, poly(lactic-co-glycolic acid) (PLGA), wound dressing

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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: 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: Mohamed A. Dkhil, Denis Delic, Saleh Al-Quraishy

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Coccidiosis causes considerable economic loss in the poultry industry. The current study aimed to investigate the response of goblet cells as well as the induced tissue damage during Eimeria papilata infection. Mice were infected with sporulated E. papillata oocyts. On day 5 post-infection, the fecal output was determined. Also, the jejunum was prepared for the histological, histochemical and molecular studies. Our results revealed that the intestinal coccidian infection with E. papillata induced a marked goblet cell hypoplasia and depleted mucus secretion. Also, the infection was able to alter the jejuna architecture and increased the apoptotic cells inside the villi. In addition, the real time PCR results indicated that, the inflammatory cytokines TNF-α, iNOS, IFN-y and IL-1β were significantly up-regulated. In contrast, the mRNA expression patterns of IL-6 in response to E. papillata infection did not differ significantly between control and infected mice. Moreover, the mRNA expression of TLR4 was significantly up-regulated, whereas the expression of MUC2 is significantly down-regulated upon infection. Further studies are required to understand the regulatory mechanisms of goblet cells related genes.

Keywords: goblet cells, Eimeria papillata, mice, jejunum

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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

Abstract:

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

Abstract:

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

Abstract:

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

Abstract:

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

Abstract:

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

Abstract:

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

Abstract:

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

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

Abstract:

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

Procedia PDF Downloads 617

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

Procedia PDF Downloads 66