Search results for: inflammatory bowel disease

Authors: Franco Van De Velde, Debora Esposito, Maria E. Pirovani, Mary A. Lila

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The physiology of various inflammatory diseases is a complex process mediated by inflammatory and immune cells such as macrophages and monocytes. Chronic inflammation, as observed in many cardiovascular and autoimmune disorders, occurs when the low-grade inflammatory response fails to resolve with time. Because of the complexity of the chronic inflammatory disease, major efforts have focused on identifying novel anti-inflammatory agents and dietary regimes that prevent the pro-inflammatory process at the early stage of gene expression of key pro-inflammatory mediators and cytokines. The ability of the extracts of three blackberry cultivars (‘Jumbo’, ‘Black Satin’ and ‘Dirksen’), and one strawberry cultivar (‘Camarosa’) to inhibit four well-known genetic biomarkers of inflammation: inducible nitric oxide synthase (iNOS), cyclooxynase-2 (Cox-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an in vitro lipopolysaccharide-stimulated murine RAW 264.7 macrophage model were investigated. Moreover, the effect of latter extracts on the intracellular reactive oxygen species (ROS) and nitric oxide (NO) production was assessed. Assay was conducted with 50 µg/mL crude extract concentration, an amount that is easily achievable in the gastrointestinal tract after berries consumption. The mRNA expression levels of Cox-2 and IL-6 were reduced consistently (more than 30%) by extracts of ‘Jumbo’ and ‘Black Satin’ blackberries. Strawberry extracts showed high reduction in mRNA expression levels of IL-6 (more than 65%) and exhibited moderate reduction in mRNA expression of Cox-2 (more than 35%). The latter behavior mirrors the intracellular ROS production of the LPS stimulated RAW 264.7 macrophages after the treatment with blackberry ‘Black Satin’ and ‘Jumbo’, and strawberry ‘Camarosa’ extracts, suggesting that phytochemicals from these fruits may play a role in the health maintenance by reducing oxidative stress. On the other hand, effective inhibition in the gene expression of IL-1β and iNOS was not observed by any of blackberry and strawberry extracts. However, suppression in the NO production in the activated macrophages among 5–25% was observed by ‘Jumbo’ and ‘Black Satin’ blackberry extracts and ‘Camarosa’ strawberry extracts, suggesting a higher NO suppression property by phytochemicals of these fruits. All these results suggest the potential beneficial effects of studied berries as functional foods with antioxidant and anti-inflammatory roles. Moreover, the underlying role of phytochemicals from these fruits in the protection of inflammatory process will deserve to be further explored.

Keywords: cyclooxygenase-2, functional foods, interleukin-6, reactive oxygen species

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Authors: Asma Naseer Cheema, Attya Bhatti, Jabar Ali, John Peter

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Background: High cholesterol levels, endothelial dysfunction, inefficient coagulation cascade and hyper inflammatory response all are the basis of coronary artery disease (CAD). Several studies are carried out to see the genetic influence of these factors on disease outcome. Objective: The objective of our study was to see the association of 10 putative loci with coronary artery disease in our population. Materials & Methods: We screened our population for 10 putative loci of CAD showing significant association (p < 5x10-8) with candidate genes (regulating the cholesterol metabolism, endothelial function, coagulation cascade and inflammatory response of body). Hardy-Weinberg equilibrium and linkage disequilibrium in cases and controls s were estimated separately. Approximately 5-10 ng of dried DNA in 384 well plate format was used to genotype each sample on the Sequenom iPLEX assay at University of Pittsburgh Genomics and Proteomics Core Laboratories. It was built on single-base primer extension with the MALDI-TOF MS detection possessing high sensitivity and specificity. The SNPs were genotyped through Taqman assay. Hardy Weinberg test was applied. The 10 SNPs were selected as genetic markers for this study (rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650). Results: Mean age of the patient was 52 ± 11 years. Blood pressure and positive family history was found a significant risk factor for CAD. None of the selected SNPs showed significant association with coronary artery disease in our population (p>0.05). Conclusion: rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650 are not significant genetic markers for CAD in our population.

Keywords: CAD, genetic markers, loci, risk factors

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Authors: S. Nasri, G. H. Amin, A. Azimi

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The use of herbs to treat disease is accompanied with the history of human life. This research is aimed to study the anti-inflammatory and antinociceptive effects of hydroalcoholic extract of aerial parts of "Tanacetum balsamita balsamita". In the experimental studies 144 male mice are used. In the inflammatory test, animals were divided into six groups: Control, positive control (receiving Dexamethason at dose of 15mg/kg), and four experimental groups receiving Tanacetum balsamita balsamita hydroalcoholic extract at doses of 25, 50, 100 and 200mg/kg. Xylene was used to induce inflammation. Formalin was used to study the nociceptive effects. Animals were divided into six groups: control group, positive control group (receiving morphine) and four experimental groups receiving Tanacetum balsamita balsamita (Tb.) hydroalcoholic extract at doses of 25, 50, 100 and 200mg/kg. I.p. injection of drugs or normal saline was performed 30 minutes before test. The data were analyzed by using one way Variance analysis and Tukey post-test. Aerial parts of Tanacetum balsamita balsamita hydroalcoholic extract decreased significantly inflammatory at dose of 200mg/kg (P<0/001) and caused a significant decrease and alleviated the nociception in both first and second phases at doses of 200mg/kg (p<0/001) and 100mg/kg (P<0/05). Tanacetum balsamita balsamita extract has the anti-inflammatory and anti-nociceptive effects which seems to be related with flavonoids especially Quercetin.

Keywords: inflammation, nociception, hydroalcoholic extract, aerial parts of Tanacetum balsamita balsamita L.

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Authors: Husham Bayazed

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Purpose of Presentation: The eye is one of a few sites in the body with immune privilege (IP). However, this IP is relatively easily bypassed in the face of sufficient strong local or systemic immunological responses. As immune responses are crucial elements of the repair response, the eye has developed distinct mechanisms to deliver immune responses to injury in the avascular regions of the eye. This presentation may cover and provide an overview of the mechanisms that dictate immune cell trafficking to the local ocular microenvironment in response to different autoimmune and inflammatory-mediated diseases. Recent Findings: Literature reviews declare that immune responses and inflammation play a key role in a diverse range of eye diseases. In recent years, our understanding of ocular immune responses has widely spread in ocular surface inflammation, uveitis, age-related macular degeneration (AMD), glaucoma, transplantation rejection, and other ocular diseases. It is becoming increasingly clear that multiple seemingly unrelated diseases involve immune responses with common themes in their ocular pathogenesis. Recent studies are focusing on elucidating the pathogenesis of ocular inflammatory disease to identify new targets for immunotherapy that will not only improve efficacy but also minimize adverse effects from traditional therapy. Summary: While IP was believed to protect the eye from day-to-day inflammatory insults, however, it is relatively easily breached in the face of different strong local or systemic immunological and inflammatory responses. Therefore, the ocular immune response encapsulates the full range of classical and non-classical immune responses and demonstrates many features which are reflected in other tissues, but eye tissues, by modifying these responses, may reveal unexpected and novel findings which are relevant to immune responses generally. This may have therapeutic potential for new targeting immunotherapy, restoring immune tolerance in ocular autoimmune and inflammatory diseases, and preventing rejection such as stem cells, currently being considered for treatment of worldwide blinding diseases such as AMD.

Keywords: ocular diseases, immunology, immune privilege, immunotherapy

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Authors: Khadse Saurabh, Talele Gokul, Surana Sanjay

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In an endeavor to find a new class of anti-inflammatory agents, a series of novel benzamides (ab1-ab16) were synthesized by utilizing some arylideneoxazolones (az1-az4) having 2-acetyloxyphenyl substitution on their second position. Structures of these synthesized compounds were confirmed by IR, 1H-NMR, 13C NMR, and HRMS. Among the tested benzamide compounds 3ab1, 3ab2, 3ab11, and 3ab16 showed promising anti-inflammatory activity with lessened propensity to cause gastro-intestinal hypermotility and ulceration when compared with standard Indomethacin. Virtual screening was performed by docking the designed compounds into the ATP binding site of COX-2 receptor to predict if these compounds have analogous binding mode to the COX-2 inhibitor.

Keywords: benzamides, anti-inflammatory, gastro-intestinal hypermotility, ulcerogenic activity, docking

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Authors: Portia Murphy, Danica Vasic, Anoja W. Gunaratne, Encarnita Sitchon, Teresita Tugonon, Marou Ison, Antoinette Le Busque, Christelle Pagonis, Thomas J. Borody

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Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that affects an estimated 11% of the population globally with the most predominant symptoms being abdominal pain, bloating and altered bowel movements. All age groups suffer from IBS although the prevalence of IBS decreases for age groups over 50 years. Women are more likely to suffer from IBS than men. IBS can be categorized into 3 groups based on the type of altered bowel movement: diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C) and IBS with mixed bowel habit (IBS-M). The contribution of the gut microbiome to the etiology of IBS is becoming increasingly recognized with rising use of anti-microbial agents. Previous studies on vancomycin and rifaximin used as monotherapy or in combination have been conducted mainly on IBS-C and showed marked improvements in the symptoms. According to our knowledge, no studies reported using these two combinations of antibiotics for IBS-D. Here, we report a consecutive cohort of 18 patients treated with both vancomycin and rifaximin for IBS-D. These patients’ records were reviewed retrospectively. In this cohort, patients ages were between 24-74 years (mean 44 years) and 9 were female. Baseline all patients had diarrhea, 4 with mucus and one with blood. Patients reported other symptoms were abdominal pain (n=11) bloating (n=9), flatulence (n=7), fatigue (n=4) and nausea (n=3). Patients treatments were personalized according to their symptom severity and tolerability and were treated with combination of rifaximin (500 - 3000mg/d) and vancomycin (500mg - 1500mg/d) for an ongoing period. Follow-ups were conducted between 2-32 weeks’ time. Of all patients, 89% patients reported improvement of the symptoms, 1 reported no change and 1 patient’s symptoms got worse. The mechanism of action for both vancomycin and rifaximin involves the inhibition of bacterial cell wall and protein synthesis respectively. The role of these medications in improving the symptoms of this cohort suggests that IBS-D may be microbiome infection driven. In this cohort, similar patient presentations to Clostridium difficile, as well as symptom improvement with the use of rifaximin and particularly vancomycin, suggest that the infectious agent may be an unidentified Clostridium. These preliminary results offer an alternative etiology for IBS-D not previously considered and open the avenue for new research.

Keywords: clostridium deficile, diarrhea predominant Irritable Bowel Syndrome, microbiome, vancomycin/rifaximin combination

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Authors: Hager Elsheikh, Matthias Sendler, Juliana Glaubnitz

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In pancreatitis, an inflammatory reaction occurs in the pancreatic secretory cells due to premature activation of proteases, leading to pancreatic self-digestion and necrotic cell death of acinar cells. Acute pancreatitis in patients is characterized by a severe immune reaction that could lead to serious complications, such as organ failure or septic shock, if left untreated. Chronic pancreatitis is a recurrence of episodes of acute pancreatitis resulting in a fibro-inflammatory immune response, in which the type 2 immune response is primarily driven by AAMs in the pancreas. One of the most important signaling pathways for M2 macrophage activation is the IL-4/STAT6 pathway. Pancreatic fibrosis is induced by the hyperactivation of pancreatic stellate cells by dysregulation in the inflammatory response, leading to further damage, autodigestion and possibly necrosis of pancreatic acinar cells. The aim of this research is to investigate the effect of STAT6 knockout in disease severity and development of fibrosis wound healing in the presence of different macrophage populations, regulated by the type 2 immune response, after inducing chronic and/or acute pancreatitis in mice models via cerulean injection. We further investigate the influence of the JAK/STAT6 signaling pathway on the balance of fibrosis and regeneration in STAT6 deficient and wild-type mice. The characterization of resident and recruited macrophages will provide insight into the influence of the JAK/STAT6 signaling pathway on infiltrating cells and, ultimately, tissue fibrosis and disease severity.

Keywords: acute and chronic pancreatitis, tissue regeneration, macrophage polarization, Gastroenterology

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Authors: Abdelrahman Abdelrahman, Lawrence Nip, Seun Ikotun, Iman Satar, Anur Miah

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Introduction: Incision and drainage of an abscess is a common procedure performed by the general surgeon. Pus swabs are often obtained routinely for MC&S.Our study aimed to investigate whether swabs taken at our local institution had any impact on the overall management plan for uncomplicated abscesses. Methods: We retrospectively assessed all patients presenting to University Hospital Lewisham with an abscess between October 2020 – April 2021. Exclusion criteria were recurrent abscesses, patients admitted with sepsis, known inflammatory bowel disease, immunocompromised, and those managed non-operatively. Results: We identified 131 patients who met the inclusion criteria. Two thirds were performed in theatre under general anaesthetic and the other one third under local. 63% of patients had a pus swab collected. Of these, 96% were not followed up by the requesting doctor, and there was no further patient contact. In the other 4%, the organisms cultured were flagged as atypical such as MRSA. In these cases, microbiology advice was that if the patient was clinically well and adequate drainage was achieved, then no furtherantibiotics were required. All patients were discharged before any microbiology results had come back with no subsequent change in the management plan. Average cost of pus swab = £10.10 – potentially cost saving of £1656.4 annually. Conclusion: Our study reveals that the majority of pus swabs taken from uncomplicated abscessesare not followed up by requesting doctor with no impact on the overall management plan. We, therefore, do not recommend the routine use of pus swabs for uncomplicated abscesses.

Keywords: pus swabs, uncomplated abscess, Pus MCS, follow up of uncomplicated abscess

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Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao

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Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2

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Authors: Uswah Ahmad Khan, Muhammad Moazam Fraz, Humayoon Shafique Satti, Qasim Aziz

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Approximately 10-14% of the global population experiences a functional disorder known as irritable bowel syndrome (IBS). The disorder is defined by persistent abdominal pain and an irregular bowel pattern. IBS significantly impairs work productivity and disrupts patients' daily lives and activities. Although IBS is widespread, there is still an incomplete understanding of its underlying pathophysiology. This study aims to help characterize the phenotype of IBS patients by differentiating the comorbidities found in IBS patients from those in non-IBS patients using machine learning algorithms. In this study, we extracted samples coding for IBS from the UK BioBank cohort and randomly selected patients without a code for IBS to create a total sample size of 18,000. We selected the codes for comorbidities of these cases from 2 years before and after their IBS diagnosis and compared them to the comorbidities in the non-IBS cohort. Machine learning models, including Decision Trees, Gradient Boosting, Support Vector Machine (SVM), AdaBoost, Logistic Regression, and XGBoost, were employed to assess their accuracy in predicting IBS. The most accurate model was then chosen to identify the features associated with IBS. In our case, we used XGBoost feature importance as a feature selection method. We applied different models to the top 10% of features, which numbered 50. Gradient Boosting, Logistic Regression and XGBoost algorithms yielded a diagnosis of IBS with an optimal accuracy of 71.08%, 71.427%, and 71.53%, respectively. Among the comorbidities most closely associated with IBS included gut diseases (Haemorrhoids, diverticular diseases), atopic conditions(asthma), and psychiatric comorbidities (depressive episodes or disorder, anxiety). This finding emphasizes the need for a comprehensive approach when evaluating the phenotype of IBS, suggesting the possibility of identifying new subsets of IBS rather than relying solely on the conventional classification based on stool type. Additionally, our study demonstrates the potential of machine learning algorithms in predicting the development of IBS based on comorbidities, which may enhance diagnosis and facilitate better management of modifiable risk factors for IBS. Further research is necessary to confirm our findings and establish cause and effect. Alternative feature selection methods and even larger and more diverse datasets may lead to more accurate classification models. Despite these limitations, our findings highlight the effectiveness of Logistic Regression and XGBoost in predicting IBS diagnosis.

Keywords: comorbidities, disease association, irritable bowel syndrome (IBS), predictive analytics

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Authors: Lourdes Hanna, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan, Grace Imaguezegie

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Background: Degeneration of the central nervous system (CNS), also known as neurodegeneration, describes an age-associated progressive loss of the structure and function of neuronal materials, leading to functional and mental impairments. Main body: Neuroinflammation contributes to the continuous worsening of neurodegenerative states which are characterised by functional and mental impairments due to the progressive loss of the structure and function of neu-ronal materials. Some of the most common neurodegenerative diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Whilst neuroinflammation is a key contributor to the progression of such disease states, it is not the single cause as there are multiple factors which contribute. Theoretically, non-steroidal anti-inflammatory drugs (NSAIDs) have potential to target neuroinflammation to reduce the severity of disease states. Whilst some animal models investigating the effects of NSAIDs on the risk of neurodegenerative diseases have shown a beneficial effect, this is not the same finding. Conclusion: Further investigation using more advanced research methods is required to better understand neuroinflammatory pathways and understand if there is still a potential window for NSAID efficacy.

Keywords: intervention, central nervous system, neurodegeneration, neuroinflammation

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Authors: Kun Chun, Jin-Chun Heo, Sang-Han Lee

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Asthma is a chronic airway inflammatory disease characterized by the infiltration of inflammatory cells and tissue remodeling. In this study, we examined the anti-asthmatic activity of a derivative of L-allo threonine by in vitro and in vivo anti-asthmatic assays. Ovalbumin (OVA)-induced C57BL/6 mice were used to analyze lung inflammation and cytokine expressions for exhibiting anti-atopic activity of the derivative. LX519290, a derivative of L-allo threonine, induced an increased IFN-γ and a decreased IL-10 mRNA level. This compound exhibited potent anti-asthmatic activity by decreasing immune cell infiltration in the lung, and IL-4 and IL-13 cytokine levels in the serum of OVA-induced mice. These results indicated that chronic airway injury was decreased by LX519290. We also assessed that LX519290 inhibits infiltration of immune cell, mucus release and cytokine expression in an in vivo model. Our results collectively suggest that the L-allo threonine is effective in alleviating asthmatic symptoms by treating inflammatory factors in the lung.

Keywords: asthma, L -allo threonine, LX519290, mice

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Authors: Agustyas Tjiptaningrum, Intanri Kurniati, Fadilah Fadilah, Linda Erlina, Tiwuk Susantiningsih

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Coronavirus disease-19 (COVID-19) is still one of the health problems. It can be a severe condition that is caused by a cytokine storm. In a cytokine storm, several proinflammatory cytokines are released massively. It destroys epithelial cells, and subsequently, it can cause death. The anti-inflammatory agent can be used to decrease the number of severe Covid-19 conditions. Melaleuca cajuputi is a plant that has antiviral, antibiotic, antioxidant, and anti-inflammatory activities. This study was carried out to analyze the prediction mechanism of the M. cajuputi extract from Lampung, Indonesia, as an anti-inflammatory agent for COVID-19. This study constructed a database of protein host target that was involved in the inflammation process of COVID-19 using data retrieval from GeneCards with the keyword “SARS-CoV2”, “inflammation,” “cytokine storm,” and “acute respiratory distress syndrome.” Subsequent protein-protein interaction was generated by using Cytoscape version 3.9.1. It can predict the significant target protein. Then the analysis of the Gene Ontology (GO) and KEGG pathways was conducted to generate the genes and components that play a role in COVID-19. The result of this study was 30 nodes representing significant proteins, namely NF-κβ, IL-6, IL-6R, IL-2RA, IL-2, IFN2, C3, TRAF6, IFNAR1, and DOX58. From the KEGG pathway, we obtained the result that NF-κβ has a role in the production of proinflammatory cytokines, which play a role in the COVID-19 cytokine storm. It is an important factor for macrophage transcription; therefore, it will induce inflammatory gene expression that encodes proinflammatory cytokines such as IL-6, TNF-α, and IL-1β. In conclusion, the blocking of NF-κβ is the prediction mechanism of the M. cajuputi extract as an anti-inflammation agent for COVID-19.

Keywords: antiinflammation, COVID-19, cytokine storm, NF-κβ, M. cajuputi

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Authors: Dzatur Rizqi Fathienah Syarifuddin, Isharyah Sunarno, Eddy Hartono, Siti Maisuri T. Chalid

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Introduction: The potential impact of coronavirus disease 2019 (COVID-19) on the health of expectant mothers and fetuses has strained attention. Pregnant women are considered a vulnerable category to respiratory infections. Moreover, several inflammatory cytokines are 2-100 times more abundant in COVID-19 with cytokine storms than in normal individuals; interleukin 6 (IL-6) exhibits much higher elevations. Investigating potential relationships between IL-6 serum levels and the severity of COVID-19 symptoms in pregnant women is the aim of this study. Material and Methods: Sixty-two eligible pregnant women were divided into a positive COVID-19 group (n=31) and a negative COVID-19 group (n=31) in this cross-sectional study. The research subjects were selected using consecutive sampling. The IL-6 was measured from a vein blood specimen using ELISA methods. Results: The COVID-19 positive group had a higher median IL-6 serum level (45.35 (35.15- 153.99) vs. 38.86 ± 11.43 (15.02-59.52), p=0.03) than the negative group. On the other hand, the IL-6 serum level had comparable value according to the COVID-19 symptoms severity (88.35 ± 36.14 ng/mL vs. 51.09 ± 25.48 ng/mL vs. 56.02 ± 33.20 ng/mL in moderate symptoms, mild symptoms, and asymptomatic, respectively; p=0.152). Conclusion: Although the IL-6 serum levels are not related to COVID-19 symptoms severity, an elevated of this biomarker was found in pregnant women with affected diagnoses.

Keywords: interleukin-6, pregnancy, COVID-19, several inflammatory

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Authors: Jun Yang, Ching-Liang Hsieh, Yi-Wen Lin

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Chronic inflammatory pain results from peripheral tissue injury or local inflammation to increase the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines. Transient receptor potential vanilloid 1 (TRPV1) is involved in fibromyalgia, neuropathic, and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are still unclear. We investigate the analgesic effect of EA by injecting complete Freund’s adjuvant (CFA) in the hind paw of mice to induce chronic inflammatory pain ( > 14 d). Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia was also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 2 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP (Glial fibrillary acidic protein), S100B, and RAGE (Receptor for advanced glycation endproducts) were also involved. The expression levels of these molecules were reduced in EA (electroacupuncture) and TRPV1−/−mice but not in the sham EA group. The present study demonstrated that EA or TRPV1 gene deletion reduced chronic inflammatory pain through TRPV1 and related molecules. In addition, our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation, electroacupuncture

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Authors: Irfan Abdulrahman Sheth, Sohil Pothiawala

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Dermatomyositis is an idiopathic inflammatory myopathy, traditionally characterized by a progressive, symmetrical proximal muscle weakness and pathognomonic or characteristic cutaneous manifestations. We report a case of a 60-year old Chinese female who was referred from polyclinic for allergic rash over the body after applying hair dye 3 weeks ago. It was associated with puffiness of face, shortness of breath and hoarse voice since last 2 weeks with decrease effort tolerance. She also complained of dysphagia/ myalgia with progressive weakness of proximal muscles and palpitations. She denied chest pain, loss of appetite, weight loss, orthopnea or fever. She had stable vital signs and appeared cushingoid. She was noted to have rash over the scalp/ face and ecchymosis over the right arm with puffiness of face and periorbital oedema. There was symmetrical muscle weakness and other neurological examination was normal. Initial impression was of allergic reaction and underlying nephrotic syndrome and Cushing’s syndrome from TCM use. Diagnostic tests showed high Creatinine kinase (CK) of 1463 u/l, CK–MB of 18.7 ug/l and Troponin –T of 0.09 ug/l. The Full blood count and renal panel was normal. EMG showed inflammatory myositis. Patient was managed by rheumatologist and discharged on oral prednisolone with methotrexate/ ergocalciferol capsule and calcium carb, vitamin D tablets and outpatient follow up. In some patients, cutaneous disease exists in the absence of objective evidence of muscle inflammation. Management of dermatomyositis begins with careful investigation for the presence of muscle disease or of additional systemic involvement, particularly of the pulmonary, cardiac or gastrointestinal systems, and for the possibility of an accompanying malignancy. Muscle disease and systemic involvement can be refractory and may require multiple sequential therapeutic interventions or, at times, combinations of therapies. Thus, we want to highlight to the physicians that the cutaneous disease of dermatomyositis should not be confused with allergic reaction. It can be particularly challenging to diagnose. Early recognition aids appropriate management of this group of patients.

Keywords: dermatomyositis, myopathy, allergy, cutaneous disease

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Authors: Sandeep Pandey, Nimra Habib, Ranjana Singh, Abbas Ali Mahdi

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Leukemia is a malignancy of blood that mainly affects children and young adults; while advancement in the early diagnosis will have the potential to improve the outcome of diseases. A wide range of disease including leukemia shows inflammatory signals in their pathogenesis. In a pilot study conducted in our laboratory, 52 people were screened, of which 26 had leukemia and 26 were free from any kind of malignancy. We performed the estimation of the inflammatory cytokine Interleukin-8 and it was found significantly raised in all the leukemia patients concerning healthy volunteers who participated in the study. Flow cytometry had been performed for the confirmation of leukemia and further genomic, and proteomic, analyses of the sample revealed that IL-8 levels showed a positive correlation in patients with leukemia. The results had shown constitutive secretion of interleukin-8 by leukemia cells. So, our finding demonstrated that IL-8 is considered to have a role in the pathogenesis of leukemia, and quantification of IL-8 levels in leukemia conditions might be more useful and feasible in the clinical setting for the prediction of drug responses where it may represent a putative target for innovative diagnostic toward effective therapeutic approaches. However, further research explorations in this area are needed that include a greater number of patients with all different forms of leukemia, and estimating their IL-8 levels may hold the key for the additional predictive values on the recurrence of leukemia and its prognosis.

Keywords: T-ALL, IL-8, leukemia pathogenesis, cancer therapeutics

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Authors: Rachid Kacem

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Excessive recruitment of Neutrophils into the lungs is a hallmark of several chronic inflammatory disorders such as emphysema and COPD. The resulting of this recruitment is the pathogenesis of lungs which is characterized by an imbalance between leukocyte serine proteinases mainly neutrophil elastase and the physiological inhibitors. The development of emphysema and remodeling of airway tissue occurred when neutrophil migrate into the lungs with more release of elastase and other proteolytic enzymes. Many reports have demonstrated that the extracts from medicinal plants such as Nigella sativa (L.) seeds extracts have anti-elastase activity; this is mainly due to the enrichment of the extracts with many bioactive molecules mainly phenolic compounds. Neutrophil serine proteases including human neutrophil elastase are involved in many inflammatory diseases, such as chronic obstructive pulmonary disease and emphysema. Since the current therapies for these diseases are inadequate and have numerous adverse effects, there is an acute need of potential alternative therapies. The natural protease inhibitors have received increasing attention as useful tools for potential utilization in pharmacology. This work is elucidating the most important natural phenolic substances that have been reported recently for their effectiveness as natural anti-elastase molecules, and hence, to the possibility of their use in the field of pharmaceuticals.

Keywords: medicinal plants, phenols, elastase, anti-elastase, chronic obstructive pulmonary disease, COPD, emphysema

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Authors: Hainan Chen, Jina Qing, Xiao Zhu, Ling Gao, Ampadu O. Jackson, Min Zhang, Kai Yin

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Objective: Editing macrophage activation to dampen inflammatory diseases by promoting the repolarization of inflammatory (M1) macrophages to anti-inflammatory (M2) macrophages is highly associated with mitochondrial respiration. Recent studies have suggested that mitochondrial apolipoprotein A-1 binding protein (APOA1BP) was essential for the cellular metabolite NADHX repair to NADH, which is necessary for the mitochondrial function. The exact role of APOA1BP in the repolarization of M1 to M2, however, is uncertain. Material and method: THP-1-derived macrophages were incubated with LPS (10 ng/ml) or/and IL-4 (100 U/ml) for 24 hours. Biochemical parameters of oxidative phosphorylation and M1/M2 markers were analyzed after overexpression of APOA1BP in cells. Results: Compared with control and IL-4-exposed M2 cells, APOA1BP was downregulated in M1 macrophages. APOA1BP restored the decline in mitochondrial function to improve metabolic and phenotypic reprogramming of M1 to M2 macrophages. Blocking oxidative phosphorylation by oligomycin blunts the effects of APOA1BP on M1 to M2 repolarization. Mechanistically, LPS triggered the hydration of NADH and increased its hydrate NADHX which inhibit cellular NADH dehydrogenases, a key component of electron transport chain for oxidative phosphorylation. APOA1BP decreased the level of NADHX via converting R-NADHX to biologically useful S-NADHX. The mutant of APOA1BP aspartate188, the binding site of NADHX, fail to repair oxidative phosphorylation, thereby preventing repolarization. Conclusions: Restoring mitochondrial function by increasing mitochondrial APOA1BP might be useful to improve the reprogramming of inflammatory macrophages into anti-inflammatory cells to control inflammatory diseases.

Keywords: inflammatory diseases, macrophage repolarization, mitochondrial respiration, apolipoprotein A-1 binding protein, NADHX, NADH

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Authors: Sharareh Sharifi

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In this study, the crude extracts of Virgularia gustavina were examined as antibacterial, antifungal and anti-inflammatory agent. To assess inflammation, Xylene was applied to the ear of mice. The mice of the experimental group were fed with doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg of lipid extract of chloroform and hexane as a separate group and then statistical analysis was performed on the results. Chloroform and hexane extracts of sea pen have strong anti-inflammatory effects even at low doses which is probably due to 54% arachidonic acid. Antibacterial and antifungal effects of hexane and chloroform extracts were measured with MIC and MBC methods and it is shown that chloroform extract has best activity against Staphylococcus aureus on 125 µg/ml doze in MIC method.

Keywords: sea pen (virgularia gustaviana), lipid extract, anti-inflammatory and anti-bacterial activities, fatty acid

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Authors: Hana Al-Baghaoi, Kumar Shiva Gubbiyappa, Mayuren Candasamy, Kiruthiga Perumal Vijayaraman

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Acne is a chronic inflammatory disease of the sebaceous glands characterized by areas of skin with seborrhea, comedones, papules, pustules, nodules, and possibly scarring. Propionibacterium acnes (P. acnes), plays a key role in the pathogenesis of acne. Their colonization and proliferation trigger the host’s inflammatory response leading to the production of pro-inflammatory cytokines such as interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The usage of honey and natural compounds to treat skin ailments has strong support in the current trend of drug discovery. The present study was carried out evaluate antimicrobial and anti-inflammatory potential of Doani Sidr honey and its fractions against P. acnes and to screen madecassoside alone and in combination with fractions of honey. The broth dilution method was used to assess the antibacterial activity. Also, ultra structural changes in cell morphology were studied before and after exposure to Sidr honey using transmission electron microscopy (TEM). The three non-toxic concentrations of the samples were investigated for suppression of cytokines IL 8 and TNF α by testing the cell supernatants in the co-culture of the human peripheral blood mononuclear cells (hPBMCs) heat killed P. acnes using enzyme immunoassay kits (ELISA). Results obtained was evaluated by statistical analysis using Graph Pad Prism 5 software. The Doani Sidr honey and polysaccharide fractions were able to inhibit the growth of P. acnes with a noteworthy minimum inhibitory concentration (MIC) value of 18% (w/v) and 29% (w/v), respectively. The proximity of MIC and MBC values indicates that Doani Sidr honey had bactericidal effect against P. acnes which is confirmed by TEM analysis. TEM images of P. acnes after treatment with Doani Sidr honey showed completely physical membrane damage and lysis of cells; whereas non honey treated cells (control) did not show any damage. In addition, Doani Sidr honey and its fractions significantly inhibited (> 90%) of secretion of pro-inflammatory cytokines like TNF α and IL 8 by hPBMCs pretreated with heat-killed P. acnes. However, no significant inhibition was detected for madecassoside at its highest concentration tested. Our results suggested that Doani Sidr honey possesses both antimicrobial and anti-inflammatory effects against P. acnes and can possibly be used as therapeutic agents for acne. Furthermore, polysaccharide fraction derived from Doani Sidr honey showed potent inhibitory effect toward P. acnes. Hence, we hypothesize that fraction prepared from Sidr honey might be contributing to the antimicrobial and anti-inflammatory activity. Therefore, this polysaccharide fraction of Doani Sidr honey needs to be further explored and characterized for various phytochemicals which are contributing to antimicrobial and anti-inflammatory properties.

Keywords: Doani sidr honey, Propionibacterium acnes, IL-8, TNF alpha

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Authors: Ae Ra Han, Seoung Eun Huh, Ji Yeon Kim, Joanne Kwak-Kim, Sung Ki Lee

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Objective: Prevalence of osteoporosis, cardiovascular disorders, and Alzheimer's disease rapidly increase after menopause. Immune activation and inflammation are suggested as an important pathogenesis of these serious diseases. Several pro-inflammatory cytokines are increased in women with surgical or natural menopause. However, the little is known about IL-17 producing T cells and Foxp3+ regulatory T (Treg) cells in post-menopause. Methods: A total of 34 postmenopausal women, who had no active cardiovascular, endocrine and infectious disorders were recruited as study group and healthy premenopausal women participated as controls. Peripheral blood mononuclear cells were isolated. Immuno-morphologic (CD3, CD4, CD8, CD19, CD56/CD16), intracellular cytokine (TNF-alpha, IFN-gamma, IL-10, IL-17), and Treg cell (Foxp3) studies were carried out using flow cytometry. The proportion of peripheral lymphocytes, including IL-17 producing and Foxp3+ Treg cells immune cell in each group were statistically analyzed. Results: The proportion of NK cells was significantly increased in menopausal women as compared to that of controls (P=.005). The ratios of TNF-alpha/IL-10 producing CD3+CD4+ T cells were increased in postmenopausal women. CD3+IL-17+ T cell level was higher in postmenopausal women and CD4+ Foxp3+ Treg cells was lower than that of controls. The ratios of CD3+IL-17+ T cell to CD3+Foxp3+ and to CD4+Foxp3+ Treg cells were significantly increased in postmenopausal women (P=.001). Conclusions: We found enhanced innate immunity and Th1- and Th17-mediated adaptive immunity in postmenopausal women. This may explain increasing prevalence of chronic inflammatory diseases after menopause. Further studies are needed to elucidate what factors contribute to this inflammatory shift in the postmenopause.

Keywords: inflammation, immune cell, menopause, Th17, regulatory T cell

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Authors: P. Halder, A. Zaman

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It is estimated that heart disease accounts for one in ten deaths worldwide. United States deaths due to heart disease are among the leading causes of death according to the World Health Organization. Cardiovascular diseases (CVDs) account for one in four U.S. deaths, according to the Centers for Disease Control and Prevention (CDC). According to statistics, women are more likely than men to die from heart disease as a result of strokes. A 50% increase in men's mortality was reported by the World Health Organization in 2009. The consequences of cardiovascular disease are severe. The causes of heart disease include diabetes, high blood pressure, high cholesterol, abnormal pulse rates, etc. Machine learning (ML) can be used to make predictions and decisions in the healthcare industry. Thus, scientists have turned to modern technologies like Machine Learning and Data Mining to predict diseases. The disease prediction is based on four algorithms. Compared to other boosts, the Ada boost is much more accurate.

Keywords: heart disease, cardiovascular disease, coronary artery disease, feature selection, random forest, AdaBoost, SVM, decision tree

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Authors: Asif Husain, Shah Alam Khan

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Coumarins and flavones are oxygen containing heterocyclic compounds which are present in various biologically active compounds. Both the heterocyclic rings are associated with diverse biological actions, therefore considered as an important scaffold for the design of molecules of pharmaceutical interest. Aim: To synthesize and evaluate the in vivo anti-inflammatory activity of few coumrain and flavone derivatives containing 1,4 dioxane ring system. Materials and methods: Coumarin derivatives (3a-d) were synthesized by reacting 7,8 dihydroxy coumarin (2a) and its 4-methyl derivative (2b) with epichlorohydrin/ethylene dibromide. The flavone derivatives (10a-d) were prepared by using quercetin and 3,4 dihydroxy flavones. Compounds of both the series were also evaluated for their anti-inflammatory, analgesic activity and ulcerogenicity in animal models by reported methods. Results and Discussion: The structures of all newly synthesized compounds were confirmed with the help of IR, 1H NMR, 13C NMR and Mass spectral studies. Elemental analyses data for each element analyzed (C, H, N) was found to be within acceptable range of ±0.4 %. Flavone derivatives, but in particular quercetin containing 1,4 dioxane ring system (10d) showed better anti-inflammatory and analgesic activity along with reduced gastrointestinal toxicity as compared to other synthesized compounds. The results of anti-inflammatory and analgesic activities of both the series are comparable with the positive control, diclofenac. Conclusion: Compound 10d, a quercetin derivative, emerged as a lead molecule which exhibited potent anti-inflammatory and analgesic activity with significant reduced gastric toxicity.

Keywords: analgesic, anti-inflammatory, 1, 4 dioxane, coumarin, flavone

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Authors: Shirajul Islam Khan, Muhammad Ashraful Alam Bhuiyan, Syeda Tania Begum

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Introduction: Acne vulgaris is one of the most common dermatologic conditions and affects the vast majority of people at some point during their lifetime, so effective treatment is of major importance. The failure of usual treatment modalities, teratogenic effects with some severe side effects, and resistance to P.Acne by Retinoides have been focusing on new therapeutic options for the treatment of acne. More recently, pulsed dye laser therapy has been reported to reduce acne lesion counts. The negligible morbidity of these treatment modalities and some other benefits of subsequent acne scar management lead this therapy more attractive. Objective: The objective of this study is to assess the efficacy and safety of pulsed dye laser therapy in the treatment of inflammatory acne vulgaris. Materials and Methods: A prospective clinical trial was done in the Department of Dermatology and Venereology, Combined Military Hospital (CMH), Dhaka, to find out the role of pulse dye laser in the treatment of inflammatory acne vulgaris. The study was carried out with 60 patients with mild to moderate acne vulgaris, and those were treated with pulsed dye laser therapy at baseline and after 4, 8, and 12 weeks. Results: Among 60 patients with inflammatory acne, 42(70%) were in the age group of less than 20 years, and 36(60%) were female. Regarding the number of inflammatory lesions, the baseline mean number (± SD) was 12.77 ± 4.01; after 4 weeks of treatment of inflammatory acne by pulsed dye laser was 7.80 ± 4.11; after 8 weeks of treatment, 6.10 ± 4.03 and after 12 weeks of treatment was 4.17 ± 4.02. After 4 weeks of treatment by pulse dye laser, the level of improvement was excellent at 3.3%, good at 10%, fair at 60%, and poor at 26.7%; after 8 weeks of treatment, excellent was 13.3%, good was 46.7%, the fair was 30% and poor 10% and after 12 weeks of treatment, excellent was 56.7%, good 13.3%, fair 23.3% and poor 6.7%. Regarding safety level, out of 60 patients of inflammatory acne vulgaris treated by pulsed dye laser, about 52(86.7%) patients did not observe any side effects. Conclusions: On the basis of the study results, it can be concluded that pulsed-dye laser is highly effective and well tolerated by patients in the treatment of inflammatory acne.

Keywords: pulsed-dye laser, inflammatory acne, acne vulgaris, retinoids

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Authors: Fakhrosadat Sajjadian

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In the USA, about 5% of women diagnosed with breast cancer annually are affected by Inflammatory Breast Cancer (IBC), which is a highly aggressive type of Locally Advanced Breast Cancer (LABC). It is a type of LABC that is clinically and pathologically different, known for its rapid growth, invasiveness, and ability to promote the growth of blood vessels. Almost all women are found to have lymph nodes affected upon diagnosis, while around 36% show obvious distant metastases. Even with the latest improvements in multimodality therapies, the outlook for patients with IBC remains bleak, as the average disease-free survival time is less than 2.5 years. Recent research on the genetic factors responsible for the IBC phenotype has resulted in the discovery of genes that play a role in the advancement of this illness. The development of primary human cell lines and animal models has assisted in this research. These advancements offer new possibilities for future actions in identifying and treating IBC.

Keywords: breast cancer, inflammation, diagnosis, IBC, LABC

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

Abstract:

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

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

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Authors: Swati Bhasin, Ali Ahmed, Valence Xavier, Ben Liu

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Aims: Diarrhea is a problem that is a frequent clinic referral to the gastroenterology and surgical team from the General practitioner. To establish a diagnosis, these patients undergo colonoscopy. The current practice at our district general hospital is to perform random left and right colonic biopsies. National guidelines issued by the British Society of Gastroenterology advise all patients presenting with chronic diarrhea should have an Ileoscopy as an indicator for colonoscopy completion. Our primary aim was to check if Terminal ileum (TI) biopsy is required to establish a diagnosis of inflammatory bowel disease (IBD). Methods: Data was collected retrospectively from November 2018 to November 2019. The target population were patients who underwent colonoscopies for diarrhea. Demographic data, endoscopic and histology findings of TI were assessed and analyzed. Results: 140 patients with a mean age of 57 years (19-84) underwent a colonoscopy (M: F; 1:2.3). 92 patients had random colonic biopsies taken and based on the histological results of these, 15 patients (16%) were diagnosed with IBD. The TI was successfully intubated in 40 patients, of which 32 patients had colonic biopsies taken as well. 8 patients did not have a colonic biopsy taken. Macroscopic abnormality in the TI was detected in 5 patients, all of whom were biopsied. Based on histological results of the biopsy, 3 patients (12%) were diagnosed with IBD. These 3 patients (100%) also had colonic biopsies taken simultaneously and showed inflammation. None of the patients had a diagnosis of IBD confirmed on TI intubation alone (where colonic biopsies were not done). None of the patients has a diagnosis of IBD confirmed on TI intubation alone (where colonic biopsies were negative). Conclusion: TI intubation is a highly-skilled, time-consuming procedure with a higher risk of perforation, which as per our study, has little additional diagnostic value in finding IBD for symptoms of diarrhea if colonic biopsies are taken. We propose that diarrhea is a colonic symptom; therefore, colonic biopsies are positive for inflammation if the diarrhea is secondary to IBD. We conclude that all of the IBDs can be diagnosed simply with colonic biopsies.

Keywords: biopsy, colon, IBD, terminal ileum

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Authors: Rahul Agarwal, Ashutosh Singh

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Colorectal cancer (CRC) also refers as bowel cancer or colon cancer. It involves the development of abnormal growth of cells in colon or rectum part of the body. This work leads to the development of a miRNA database in colorectal cancer. We named this database- miCoRe. This database comprises of all validated colon-rectal cancer miRNAs information from various published literature with an effectual knowledge based information retrieval system. miRNAs have been collected from various published literature reports. MySQL is used for main-framework of miCoRe while the front-end was developed in PHP script. The aim of developing miCoRe is to create a comprehensive central repository of colorectal carcinoma miRNAs with all germane information of miRNAs and their target genes. The current version of miCoRe consists of 238 miRNAs which are known to be implicated in malignancy of CRC. Alongside with miRNA information, miCoRe also contains the information related to the target genes of these miRNA. miCoRe furnishes the information about the mechanism of incidence and progression of the disease, which would further help the researchers to look for colorectal specific miRNAs therapies and CRC specific targeted drug designing. Moreover, it will also help in development of biomarkers for the better and early detection of CRC and will help in better clinical management of the disease.

Keywords: colorectal cancer, database, miCoRe, miRNAs

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Authors: Ghada M. El-Kassas, Maged A. El Wakeel, Salwa R. El-Zayat

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Background: Environmental enteric dysfunction (EED) is asymptomatic villous atrophy of the small bowel that is prevalent in the developing world and is associated with altered intestinal function and integrity. Evidence has suggested that supplementary omega-3 might ameliorate this damage by reducing gastrointestinal inflammation and may also benefit cognitive development. Objective: We tested whether omega-3 supplementation improves intestinal integrity, growth, and cognitive function in stunted children predicted to have EED. Methodology: 100 Egyptian stunted children aged 1-5 years and 100 age and gender-matched normal children as controls. At the primary phase of the study, we assessed anthropometric measures and fecal markers such as myeloperoxidase (MPO), neopterin (NEO), and alpha-1-anti-trypsin (AAT) (as predictors of EED). Cognitive development was assessed (Bayley or Wechsler scores). Oral n-3 (omega-3) LC-PUFA at a dosage of 500 mg/d was supplemented to all cases and followed up for 6 months after which the 2ry phase of the study included the previous clinical, laboratory and cognitive assessment. Results: Fecal inflammatory markers were significantly higher in cases compared to controls. (MPO), (NEO) and (AAT) showed a significant decline in cases at the end of the 2ry phase (P < 0.001 for all). Omega-3 supplementation resulted also in a significant increase in mid-upper arm circumference (MUAC) (P < 0.01), weight for age z-score, and skinfold thicknesses (P< 0.05 for both). Cases showed significant improvement of cognitive function at phase 2 of the study. Conclusions: Omega-3 supplementation successfully improved intestinal inflammatory state related to EED. Also, some improvement of anthropometric and cognitive parameters showed obvious improvement with omega-3 supplementation.

Keywords: cognitive functions, EED, omega-3, stunting

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