Search results for: idiopathic inflammatory myopathies

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

Procedia PDF Downloads 146

Authors: Nendouvhada Livhuwani Portia, Nicole Sibuyi, Kwazikwakhe Gabuza, Adewale Fadaka

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Metabolic dysfunction-associated liver disease (MASLD) is a chronic condition characterized by excessive fat accumulation in the liver, distinct from conditions caused by alcohol, viral hepatitis, or medications. MASLD is often linked with metabolic syndrome, including obesity, diabetes, hyperlipidemia, and hypertriglyceridemia. This disease can progress to metabolic dysfunction-associated steatohepatitis (MASH), marked by liver inflammation and scarring, potentially leading to cirrhosis. However, only 43-44% of patients with steatosis develop MASH, and 7-30% of those with MASH progress to cirrhosis. The exact mechanisms underlying MASLD and its progression remain unclear, and there are currently no specific therapeutic strategies for MASLD/MASH. While anti-obesity and anti-diabetic medications can reduce progression, they do not fully treat or reverse the disease. As an alternative, green-synthesized metal nanoparticles (MNPs) are emerging as potential treatments for liver diseases due to their anti-diabetic, anti-inflammatory, and anti-obesity properties with minimal side effects. MNPs like gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have been shown to improve metabolic processes by lowering blood glucose, body fat, and inflammation. The study aimed to explore the effects of green-synthesized MNPs on gene expression in an in vitro model of MASH using C3A/HepG2 liver cells. The MASH model was created by exposing these cells to free fatty acids (FFAs) followed by lipopolysaccharide (LPS) to induce inflammation. Cell viability was assessed with the Water-Soluble Tetrazolium (WST)-1 assay, and lipid accumulation was measured using the Oil Red O (ORO) assay. Additionally, mitochondrial membrane potential was assessed by the tetramethyl rhodamine, methyl ester (TMRE) assay, and inflammation was measured with an Enzyme-Linked Immunosorbent Assay (ELISA). The study synthesized AuNPs from Carpobrotus edulis fruit (CeF) and avocado seed (AvoSE) and AgNPs from Salvia africana-lutea (SAL) using optimized conditions. The MNPs were characterized by UV-Vis spectrophotometry and Dynamic Light Scattering (DLS). The nanoparticles were tested at various concentrations for their impact on the C3A/HepG2-induced MASH model. Among the MNPs tested, AvoSE-AuNPs showed the most promise. They reduced cell proliferation and intracellular lipid content more effectively than CeFE-AuNPs and SAL-AgNPs. Molecular analysis using real-time polymerase chain reaction revealed that AvoSE-AuNPs could potentially reverse MASH effects by reducing the expression of key pro-inflammatory and metabolic genes, including tumor necrosis factor-alpha (TNF-α), Fas cell surface death receptor (FAS), Peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, and Sterol regulatory element-binding protein (SREBPF)-1. Further research is needed to confirm the molecular mechanisms behind the effects of these MNPs and to identify the specific phytochemicals responsible for their synthesis and bioactivities.

Keywords: gold nanoparticles, green nanotechnology, metal nanoparticles, obesity

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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

Procedia PDF Downloads 241

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

Procedia PDF Downloads 264

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

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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

Procedia PDF Downloads 645

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

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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

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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

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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

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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: Sinead Morrison, Ann Swillen, Therese Van Amelsvoort, Samuel Chawner, Elfi Vergaelen, Michael Owen, Marianne Van Den Bree

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22q11.2 Deletion Syndrome (22q11.2DS) is caused by the deletion of approximately 60 genes on chromosome 22 and is associated with high rates of neurodevelopmental disorders such as Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD). The presentation of these disorders in 22q11.2DS is reported to be comparable to idiopathic forms and therefore presents a valuable model for understanding mechanisms of neurodevelopmental disorders. Cognitive deficits are thought to be a core feature of neurodevelopmental disorders, and possibly manifest in behavioural and emotional problems. There have been mixed findings in 22q11.2DS on whether the presence of ADHD or ASD is associated with greater cognitive deficits. Furthermore, the influence of developmental stage has never been taken into account. The aim was therefore to examine whether the presence of ADHD or ASD was associated with cognitive deficits in childhood and/or adolescence in 22q11.2DS. We conducted the largest study to date of this kind in 22q11.2DS. The same battery of tasks measuring processing speed, attention and spatial working memory were completed by 135 participants with 22q11.2DS. Wechsler IQ tests were completed, yielding Full Scale (FSIQ), Verbal (VIQ) and Performance IQ (PIQ). Age-standardised difference scores were produced for each participant. Developmental stages were defined as children (6-10 years) and adolescents (10-18 years). ADHD diagnosis was ascertained from a semi-structured interview with a parent. ASD status was ascertained from a questionnaire completed by a parent. Interaction and main effects of cognitive performance of those with or without a diagnosis of ADHD or ASD in childhood or adolescence were conducted with 2x2 ANOVA. Significant interactions were followed up with t-tests of simple effects. Adolescents with ASD displayed greater deficits in all measures (processing speed, p = 0.022; sustained attention, p = 0.016; working memory, p = 0.006) than adolescents without ASD; there was no difference between children with and without ASD. There were no significant differences on IQ measures. Both children and adolescents with ADHD displayed greater deficits on sustained attention (p = 0.002) than those without ADHD. There were no significant differences on any other measures for ADHD. Magnitude of cognitive deficit in individuals with 22q11.2DS varied by cognitive domain, developmental stage and presence of neurodevelopmental disorder. Adolescents with 22q11.2DS and ASD showed greater deficits on all measures, which suggests there may be a sensitive period in childhood to acquire these domains, or reflect increasing social and academic demands in adolescence. The finding of poorer sustained attention in children and adolescents with ADHD supports previous research and suggests a specific deficit which can be separated from processing speed and working memory. This research provides unique insights into the association of ASD and ADHD with cognitive deficits in a group at high genomic risk of neurodevelopmental disorders.

Keywords: 22q11.2 deletion syndrome, attention deficit hyperactivity disorder, autism spectrum disorder, cognitive development

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Authors: Pear-Rarin Leelakunakorn, Patompong Satapornpong

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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

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

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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

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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

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Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

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The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

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Authors: Adineh Tajmousavilangerudi, Ali Zein Alabiden Tlais, Raffaella Di Cagno

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The SARS-Cov-2 pandemic has exposed our vulnerability to new illnesses and novel viruses that attack our immune systems, particularly in the elderly. The vaccine is being gradually introduced over the world, but new strains of the virus and COVID-19 will emerge and continue to cause illness. Aging is associated with significant changes in intestinal physiology, which increases the production of inflammatory products, alters the gut microbiota, and consequently establish inadequate immune response to minimize symptoms and disease development. In this context, older people who followed a Mediterranean-style diet, rich in polyphenols and dietary fiber, performed better physically and mentally (1,2). This demonstrates the importance of the human gut microbiome in transforming complex dietary macromolecules into the most biologically available and active nutrients, which in turn help to regulate metabolism and both intestinal and systemic immune function (3,4). The role of lactic acid fermentation is prominent also as a powerful tool for improving the nutritional quality of the human diet by releasing nutrients and boosting the complex bioactive compounds and vitamin content. the PhD project aims to design fermented and functional foods/beverages capable of modulating human immune function via the gut microbiome.

Keywords: functional bevarage, fermented beverage, gut microbiota functionality, immun system

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Authors: Haralabos C. karantonis, Afroditi Michalaki

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High intakes of carbohydrates and fats have been associated with an increased risk of chronic diseases due to the role of postprandial oxidative stress. This pilot nutritional intervention aimed to examine the acute effect of consuming two different types of breadsticks prepared from durum wheat flour mixtures differing in total phenolic content on postprandial inflammatory and oxidant responses in healthy volunteers. A cross-over, controlled, and single-blind clinical trial was designed, and two isocaloric high-fat and high-carbohydrate meals were tested. Serum total, High Density Lipoprotein (HDL)- and Low Density Lipoprotein (LDL)-cholesterol, triglycerides, glucose, C-reactive protein (CRP), uric acid, plasma total antioxidant capacity, and antiplatelet activity were determined in fasting and 30, 60, and 120 min after consumption. The results showed a better postprandial HDL-cholesterol and total antioxidant activity response in the intervention group. The choice of durum wheat flours with higher phenolic content and antioxidant activity is presented as promising for human health, and clinical studies will expand to draw safer conclusions.

Keywords: antioxidant, antiplatelet, durum wheat, nutritional value

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Authors: Kambiz Hassanzadeh, Seyedeh Shohreh Ebrahimi, Shahrbanoo Oryan, Arman Rahimmi, Esmael Izadpanah

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Parkinson’s disease is one of the most prevalent neurodegenerative diseases which occurs in elderly. There are convincing evidences that oxidative stress has an important role in both the initiation and progression of Parkinson’s disease. Thymoquinone (TQ) is shown to have antioxidant and anti-inflammatory properties in invitro and invivo studies. It is well documented that TQ acts as a free radical scavenger and prevents the cell damage. Therefore this study aimed to evaluate the effect of TQ on motor and non-motor symptoms in animal model of Parkinson’s disease. Male Wistar rats (10-12 months) received rotenone (1mg/kg/day, sc) to induce Parkinson’s disease model. Pretreatment with TQ (7.5 and 15 mg/kg/day, po) was administered one hour before the rotenone injection. Three motor tests (rotarod, rearing and bar tests) and two non-motor tests (forced swimming and elevated plus maze) were performed for behavioral assessment. Our results indicated that TQ significantly ameliorated the rotenone-induced motor dysfunction in rotarod and rearing tests also it could prevent the non-motor dysfunctions in forced swimming and elevated plus maze tests. In conclusion we found that TQ delayed the Parkinson's disease induction by rotenone and this effect might be related to its proved antioxidant effect.

Keywords: Parkinson's disease, thymoquinone, motor and non-motor symptoms, neurodegenerative disease

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Authors: Subrata Kar, Banani Kundu, Papiya Nandy, Ruma Basu, Sukhen Das

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Natural montmorilollite clay is a common ingredient in pharmaceutical products, both as excipients and active support; hence considered as suitable candidate for Drug Delivery System. In this work, cationic detergent CTAB is used to increase the interlayer spacing of Na+-Montmoriollite clay to intercalate curcumin and methotrexate. Methotrexate is a folic acid antagonist, anti-proliferative and immunosuppressive agent; while curcumin is a bioactive constituent of rhizomes of Curcuma longa, possessing remarkable chemo-preventive and anti-inflammatory properties. The resultant inorganic-organic hybrids are characterized by X-ray diffraction (XRD), Infrared spectroscopy (FTIR) and Thermo Gravimetric Analysis (TGA) to confirm successful intercalation of curcumin and Methotrexate within clay layers. Pharmaceutical investigation of the hybrids is explored by studying the drug loading (%), encapsulation efficiency and release kinetics. Finally in-vitro studies are performed using cancer cells to find the effect of released curcumin to improve the sensitivity of clay bound methotrexate to ameliorate cell death compared to their effectiveness when used without the inorganic aluminosilicate vehicle.

Keywords: montmorillonite, methotrexate, curcumin, loading efficiency, release kinetics, anticancer activity

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Authors: Santhita Tungkajiwangkoon, Yoshikazu Hoshi

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Three Japaneses Drosera species are the good model to study genome organization with highly specialized morphological group for insect trapping, and has revealed anti-inflammatory, and antibacterial effects, so there must be a reason for botanists are so appealing in these plants. Cytology and Flow cytometry were used to investigate the genetic stability and ploidy estimation in three related species. The cytological and Flow cytometry analysis were done in Drosera rotundifolia L., Drosera spatulata Labill and Drosera tokaiensis. The cytological studies by fluorescence staining (DAPI) showed that D. tokaiensis was an alloploid (2n=6x=60, hexaploid) which is a natural hybrid polyploids of D. rotundifolia and D. spatulata. D. rotundifolia was a diploid with the middle size of metaphase chromosomes (2n=2x=20) as a paternal origin and D. spatulata was a tetraploid with small size of metaphase chromosome (2n=4x=40) as a maternal origin. We confirmed by Flow cytometry analysis to determine the ploidy level and DNA content of the plants. The 2C-DNA values of D. rotundiflolia were 2.8 pg, D. spatulata was 1.6 pg and D. tokaiensis was 3.9 pg. However, 2C- DNA values of D. tokaiensis should be related from their parents but in the present study the 2C-DNA values of D. tokaiensis was no relation from the theoretical of hybrids representing additive parental. Possibility of D. tokaiensis is a natural hybrid, which is also hybridization in natural evolution can cause the genome reduction in plant.

Keywords: drosera, hybrid, cytology, flow cytometry

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Authors: Santosh Tummidi, Pragati Sathe, Kanchan Kothari, Prachi Gholap, Mona Agnihotri, Gwendolyn Fernandes, Leena Naik, Rachana Chaturvedi

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Introduction: EUS-Guided Fine Needle Aspiration/Brush (EUS-FNA/Brush) has become increasingly popular for the diagnosis and staging of gastrointestinal and peri-gastrointestinal lesions. Objective: To evaluate the diagnostic accuracy and spectrum of lesions in gastrointestinal EUS-FNA. Material and Methods: A total of 124 EUS-FNA during the period from Aug 2015-Nov 2016 were studied. Results: Age ranged from 13-80 years with a slight female predominance. CBD was the most common site with 47 cases amongst which were 9 adenocarcinoma, and 7 cases were suspicious for malignancy. Pancreatic EUS-FNA showed 5 adenocarcinoma, 2 SPEN, 1 case each of neuroendocrine tumor, anaplastic carcinoma and NHL. Amongst oesophageal lesions, 3 cases were suspicious for malignancy, and 4 were inflammatory, 4 showed SCC, 1case each adenocarcinoma and leiomyoma. Stomach- 1 case each of adenocarcinoma, granulomatous inflammation, and GIST. Periportal lymph nodes were the commonest nodes, and there were 11 necrotising granulomatous inflammations, 3 metastatic adenocarcinoma, 2 cases of atypical cells and 1 case of NHL. 17 cases were unsatisfactory, 41 cases had histopathology follow up with 85% cases being concordant. Conclusion: EUS-FNA is reliable, sensitive and specific. It can be utilized for better management of intra-abdominal lesions.

Keywords: EUS-FNA, brush, cytology, histopathology

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Authors: Hamid Hossein Khezri, Afsaneh Javdani-Mallak

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Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Cannabidiol (CBD) is one of the members of cannabinoid compounds found in cannabis. CBD and Cannabinol (CBN), as the other extract of plant Cannabis were able to reduce myofascial pain in rats with immunosuppressive and anti-inflammatory activities. In this study, we accomplished protein-protein BLAST, and the sequence was found to be for Gamma-aminobutyric acid receptor subunit alpha-1 (GBRA1) chain A and its 3D structure was subsequently downloaded from Protein Data Bank. The structures of the ligands, cannabinol, and cannabidiol, were obtained from PubChem. After the necessary process of the obtained files, AutoDock Vina was used to perform molecular docking. Docking between the ligands and GBRA1 chain A revealed that cannabinol has a higher affinity to GBRA1 (binding energy = -7.5 kcal/mol) compared to cannabidiol (binding energy = -6.5 kcal/mol). Furthermore, cannabinol seems to be able to interact with 10 residues of the protein, out of which 3 are in the neurotransmitter-gated ion-channel transmembrane domain of GBRA1, whereas cannabidiol interacts with two other residues. Although the results of this project do not indicate the activating /or inhibitory capability of the studied compounds, it suggests that cannabinol can act as a relatively strong ligand for GBRA1.

Keywords: protein-ligand docking, cannabinol, cannabidiol, GBRA1

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Authors: Beverly Wang

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Background: Rosai-Dorfman disease (RDD), aka sinus histiocytosis with massive lymphadenopathy, is a rare, idiopathic histiocytic proliferative disorder. Although RDD can be seen involving the head and neck lymph nodes, rarely it can affect other extranodal sites. It present 3 unique cases of RDD affecting the nasal cavity, paranasal sinuses, and ear canal. The initial clinical presentation on two cases mimicked a malignant neoplasm. The 3rd case of RDD co-existed with a cholesteatoma of the ear canal. The clinical presentation, histology and immunohistochemical stains, and radiographic findings are discussed. Design: An overview of 3 cases of RDD affected sinonasal cavity and ear canal from UCI Medical Center was conducted. Case 1: A 61 year old male complaining of breathing difficulty presented with bilateral polypoid sinonasal masses and severe nasal obstruction. The masses elevated the nasal floor, and involved the anterior nasal septum to lateral wall. It was endoscopically excised. At intraoperative consultation, frozen section reported a pleomorphic spindle cell neoplasm with scattered large atypical spindle cells, resembling a high grade sarcoma. Case 2: A 46 year old male presented with recurrent bilateral maxillary chronic sinusitis with mass formation, clinically suspicious for malignant lymphoma. Excisional tissue sample showed large irregular spindled histiocytes with abundant granular and vacuolated cytoplasm. Case 3: A 36 year old female with a history of asthma initially presented with left-sided chronic otalgia, occasional nausea, vertigo, and fluctuating pain exacerbated by head movement and temperature changes. CT scan revealed an external auditory canal mass extending to the middle ear, coexisting with a small cholesteatoma. Results: The morphology of all cases revealed large atypical spindled histiocytes resembling fibrohistiocytic or myofibroblastic proliferative neoplasms. Scattered emperipolesis was seen. All 3 cases were confirmed as extranodal sinus RDD, confirmed by immunohistochemistry. The large atypical cells were positive for S100, CD68, and CD163. No evidence for malignancy was identified. Case 3 showed concurrent RDD co-existing with a cholesteatoma. Conclusion: Due to its rarity and variable clinical presentations, the diagnosis of RDD is seldom clinically considered. Extranodal sinus RDD morphologically can be pitfall as mimicker of spindly neoplasm, especially at intraoperative consultation. It can create diagnostic and therapeutic challenges. Correlation of radiological findings with histologic features will help to reach the diagnosis.

Keywords: head and neck, extranodal, rosai-dorfman disease, mimicker, immunohistochemistry

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Authors: Eun Young Choi, So Hui Choe, Jin Yi Hyeon, Ji Young Jin, Bo Ram Keum, Jong Min Lim, Hyung Rae Cho, Kwang Keun Cho, In Soon Choi

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This research analyzed the effect of β-glucan that is expected to alleviate the production of inflammatory mediator in macrophagocyte, which was processed by the lipopolysaccharide (LPS) of Escherichia, a pathogen related to allergy. The incubated layer was used for nitric oxide (NO) analysis. The DNA-binding activation of the small unit of NF-κB was measured using ELISA-based kit. In RAW264.7 cells that were vitalized by E.coli LPS, β-glucan inhibited both the combatant and rendering phases of inducible NO synthase (iNOS)-derived NO. β-glucan increased the expression of heme oxygenase-1 (HO-1) in the cell that was stimulated by E.coli LPS, and HO-1 activation was inhibited by SnPP. This shows that NO production induced by LPS is related to the inhibition effect of β-glucan. The phosphorylation of JNK and p38 induced by LPS were not influenced by β-glucan, and IκB-α decomposition was not influenced either. Instead, β-glucan remarkably inhibited the phosphorylation of STAT1 that was induced by E.coli LPS. Overall, β-glucan inhibited the production of NO in macrophagocyte that was vitalized by E.coli LPS through HO-1 induction and STAT1 pathways inhibition in this research. As the host inflammation reaction control by β-glucan weakens the progress of allergy, β-glucan can be used as an effective treatment method.

Keywords: β-glucan, lipopolysaccharide (LPS), nitric oxide (NO), RAW264.7 cells, STAT1

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Authors: Ezeh Chukwunonso Peter Excel, Akruti Vg

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Aim/Background: To show that even after undergoing 1-5 courses of chemotherapy for Gestational Trophoblastic Disease (GTD) reproductive health of women is intact and they conceive successfully after it. Method: Retrospective cohort analysis using data from the Lugansk regional maternity hospital database of years 1993-2013, which shows n=18 females had GTD and underwent 1-5 courses of chemotherapy. Results and Discussion: Frequency of GTD was rare. All 18 patients (pts) belong to age group of 17-39 years, covering wide range of reproductive age. Out of 18 pts, 15 had hydatidiform mole (HM) while other 3 had choriocarcinoma (CC). In anamnesis, among CC pts, 1 had early pre-eclampsia at 24 weeks and 1 had 4th week of late postpartum (PP) bleeding, while all HM pts had genital inflammatory diseases, 1 pt of HM during follow-up had High hCG and 3 times curettage in 5 months. 18 women became pregnant for 25 times after chemotherapy. Chemotherapy was given under indication of either high level of HCG, luteal cyst >6cm or path-morphological results of curettage. CC 3 pts had (2 spontaneous abortions (SA), 2 term cesarean section (CS), 1 preterm CS). HM 15 pts had (3 artificial abortion, 2 SA, 7CS (5 term and 2 preterm), 8 vaginal deliveries (7 term and 1 preterm)). Conclusion: During our research we got 22.2% preterm deliveries and 55.6% CS which is higher than the normal cases, but still all the 18 women were able to have kids successfully after chemotherapy. So we can conclude that chemotherapy for GTD was successful in keeping the reproductive health of women intact.

Keywords: reproductive health, chemotherapy, gestational trophoblastic disease, women

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