Search results for: inflammatory cytokine

Authors: Mustafa M. Donma, Orkide Donma

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Iron is physiologically essential. However, it also participates in the catalysis of free radical formation reactions. Its deficiency is associated with amplified health risks. This trace element establishes some links with another physiological process related to cell death, apoptosis. Both iron deficiency and iron overload are closely associated with apoptosis. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has the ability to trigger apoptosis and plays a dual role in the physiological versus pathological inflammatory responses of tissues. The aim of this study was to investigate the status of these parameters as well as the associations among them in children with obesity, a low-grade inflammatory state. The study was performed on groups of children with normal body mass index (N-BMI) and obesity. Forty-three children were included in each group. Based upon age- and sex-adjusted BMI percentile tables prepared by World Health Organization, children whose values varied between 85 and 15 were included in N-BMI group. Children whose BMI percentile values were between 99 and 95 comprised obese (OB) group. Institutional ethical committee approval and informed consent forms were taken prior to the study. Anthropometric measurements (weight, height, waist circumference, hip circumference, head circumference, neck circumference) and blood pressure values (systolic blood pressure and diastolic blood pressure) were recorded. Routine biochemical analysis including serum iron, total iron binding capacity (TIBC), transferrin saturation percent (Tf Sat %), and ferritin were performed. Soluble tumor necrosis factor-like weak inducer of apoptosis levels were determined by enzyme-linked immunosorbent assay. Study data was evaluated using appropriate statistical tests performed by the statistical program SPSS. Serum iron levels were 91±34 mcrg/dl and 75±31 mcrg/dl in N-BMI and OB children, respectively. The corresponding values for TIBC, Tf Sat %, ferritin were 265 mcrg/dl vs 299 mcrg/dl, 37.2±19.1 % vs 26.7±14.6 %, and 41±25 ng/ml vs 44±26 ng/ml. in N-BMI and OB groups, sTWEAK concentrations were measured as 351 ng/L and 325 ng/L, respectively (p>0.05). Correlation analysis revealed significant associations between sTWEAK levels and iron related parameters (p<0.05) except ferritin. In conclusion, iron contributes to apoptosis. Children with iron deficiency have decreased apoptosis rate in comparison with that of healthy children. sTWEAK is inducer of apoptosis. Obese children had lower levels of both iron and sTWEAK. Low levels of sTWEAK are associated with several types of cancers and poor survival. Although iron deficiency state was not observed in this study, the correlations detected between decreased sTWEAK and decreased iron as well as Tf Sat % values were valuable findings, which point out decreased apoptosis. This may induce a proinflammatory state, potentially leading to malignancies in the future lives of obese children.

Keywords: apoptosis, children, iron-related parameters, obesity, soluble tumor necrosis factor-like weak inducer of apoptosis

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Authors: A. N.Ukwuani, A. K. Abdulfatah

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G. crenata is used locally for the treatment of fractured bones, wound healing and inflammatory conditions. In vitro and in vivo antioxidant activity of hydromethanolic extracts of the leaves of G. crenata were assessed. The phytochemical analysis shows the presence of phenols, flavonoids, saponins, cardiac glycosides and tannins. An in vitro quantitative analysis of phenols, flavonoids and tannins respectively were (164±1.20, 199±0.88 and 88.67±0.88 mg/100g FW). In vivo studies of hydromethanolic extract demonstrated a dose dependent increase in hepatic superoxide dismutase (1.14±0.14, 2.13±0.11, 2.55±0.11 U/mg Protein) with improvement in hepatic glutathione (6.98±0.42, 8.91±0.37, 11.07±0.46 µM/mg Protein) and Catalase (4.47±0.05, 6.24±0.02, 7.17±0.04 U/mg Protein) and Total protein (6.18±0.08, 6.69±0.18, 7.27±0.16 mg/ml) respectively at 100-300mg/kg body weight Grewia crenata leaves when compared to the control and standard drug. It can be concluded from the present findings of that G. crenata leaves possess antioxidant potential.

Keywords: Grewia crenata, antioxidant, hydromethanolic extract, in vivo, in vitro

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Authors: Stavros Poulopoulos, Aphrodite Tetorou, Constantine Philippopoulos

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Day after day more pharmaceutical compounds that are not efficiently removed by conventional treatment methods are found in treated wastewaters and drinking waters. Due to their refractory nature, they escape conventional wastewater treatment facilities, and thus advanced oxidation processes have to be utilized to effectively eliminate them. In the present study, the removal of Ibuprofen from aqueous solutions containing the commercial drug Algofren (non-steroidal, anti-inflammatory) using UV irradiation, hydrogen peroxide, titanium dioxide and ferric ions was examined. All experiments were conducted in a batch photoreactor operated for 120 min. The main target was to select the most effective operating conditions for the mineralization of the solutions treated. The combination of Fe(III)/ H₂O₂/UV proved to be very efficient in terms of total organic carbon removal and ibuprofen conversion. For solutions containing 5 mg/L ibuprofen and initial total carbon 51.1 mg/L, complete mineralization was achieved by means of 2.2 ppm Fe(III) and 333 mg/L H₂O₂.

Keywords: pharmaceuticals, photocatalytic, photo-Fenton, TiO₂

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Authors: N. Zeinalzadeh, Mahdi Sadeghi

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Enterotoxigenic Escherichia coli (ETEC) is the most common cause of non-inflammatory diarrhea in the developing countries, resulting in approximately 20% of all diarrheal episodes in children in these areas. ST is one of the most important virulence factors and CFA/I is one of the frequent colonization factors that help to process of ETEC infection. ST and CfaB (CFA/I subunit) are among vaccine candidates against ETEC. So, ST because of its small size is not a good immunogenic in the natural form. However to increase its immunogenic potential, here we explored candidate positions for ST insertion in CfaB sequence. After bioinformatics analysis, one of the candidate positions was selected and the chimeric gene (cfaB*st) sequence was synthesized and expressed in E. coli BL21 (DE3). The chimeric recombinant protein was purified with Ni-NTA columns and characterized with western blot analysis. The residue 74-75 of CfaB sequence could be a good candidate position for ST and other epitopes insertion.

Keywords: bioinformatics, CFA/I, enterotoxigenic E. coli, ST toxoid

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Authors: Ruqaiya Khalil, Saman Usmani, Zaheer Ul-Haq

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The accurate characterization of ligand binding affinity is indispensable for designing molecules with optimized binding affinity. Computational tools help in many directions to predict quantitative correlations between protein-ligand structure and their binding affinities. Molecular dynamics (MD) simulation is a modern state-of-the-art technique to evaluate the underlying basis of ligand-protein interactions by characterizing dynamic and energetic properties during the event. Autoimmune diseases arise from an abnormal immune response of the body against own tissues. The current regimen for the described condition is limited to immune-modulators having compromised pharmacodynamics and pharmacokinetics profiles. One of the key player mediating immunity and tolerance, thus invoking autoimmunity is Interleukin-2; a cytokine influencing the growth of T cells. Molecular dynamics simulation techniques are applied to seek insight into the inhibitory mechanisms of newly synthesized compounds that manifested immunosuppressant potentials during in silico pipeline. In addition to estimation of free energies associated with ligand binding, MD simulation yielded us a great deal of information about ligand-macromolecule interactions to evaluate the pattern of interactions and the molecular basis of inhibition. The present study is a continuum of our efforts to identify interleukin-2 inhibitors of both natural and synthetic origin. Herein, we report molecular dynamics simulation studies of Interluekin-2 complexed with different antagonists previously reported by our group. The study of protein-ligand dynamics enabled us to gain a better understanding of the contribution of different active site residues in ligand binding. The results of the study will be used as the guide to rationalize the fragment based synthesis of drug-like interleukin-2 inhibitors as immune-modulators.

Keywords: immuno-modulators, MD simulation, protein-ligand interaction, structure-based drug design

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Authors: Marina Shargorodsky

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Aim: Gestational weight gain (GWG) has been related to altering future weight-gain curves and increased risks of obesity later in life. Obesity may contribute to vascular atherosclerotic changes as well as excess cardiovascular morbidity and mortality observed in these patients. Noninvasive arterial testing, such as ultrasonographic measurement of carotid IMT, is considered a surrogate for systemic atherosclerotic disease burden and is predictive of cardiovascular events in asymptomatic individuals as well as recurrent events in patients with known cardiovascular disease. Currently, there is no consistent evidence regarding the vascular impact of excessive GWG. The present study was designed to investigate the impact of GWG on early atherosclerotic changes during late pregnancy, using intima-media thickness, as well as placental vascular circulation and inflammatory lesions and pregnancy outcomes. Methods: The study group consisted of 59 pregnant women who gave birth and underwent a placental histopathological examination at the Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Israel, in 2019. According to the IOM guidelines the study group has been divided into two groups: Group 1 included 32 women with pregnancy weight gain within recommended range; Group 2 included 27 women with excessive weight gain during pregnancy. The IMT was measured from non-diseased intimal and medial wall layers of the carotid artery on both sides, visualized by high-resolution 7.5 MHz ultrasound (Apogee CX Color, ATL). Placental histology subdivided placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion according to the criteria of the Society for Pediatric Pathology, subdividing placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion, as well as the inflammatory response of maternal and fetal origin. Results: IMT levels differed between groups and were significantly higher in Group 1 compared to Group 2 (0.7+/-0.1 vs 0.6+/-0/1, p=0.028). Multiple linear regression analysis of IMT included variables based on their associations in univariate analyses with a backward approach. Included in the model were pre-gestational BMI, HDL cholesterol and fasting glucose. The model was significant (p=0.001) and correctly classified 64.7% of study patients. In this model, pre-pregnancy BMI remained a significant independent predictor of subclinical atherosclerosis assessed by IMT (OR 4.314, 95% CI 0.0599-0.674, p=0.044). Among placental lesions related to fetal vascular malperfusion, villous changes consistent with fetal thrombo-occlusive disease (FTOD) were significantly higher in Group 1 than in Group 2, p=0.034). In Conclusion, the present study demonstrated that excessive weight gain during pregnancy is associated with an adverse effect on early stages of subclinical atherosclerosis, placental vascular circulation and neonatal complications. The precise mechanism for these vascular changes, as well as the overall clinical impact of weight control during pregnancy on IMT, placental vascular circulation as well as pregnancy outcomes, deserves further investigation.

Keywords: obesity, pregnancy, complications, weight gain

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Authors: Yoshino Murakami, Takeshi Hashimoto, Steve Cole

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The autonomic nervous system (ANS), particularly the sympathetic (SNS) and parasympathetic (PNS) branches, plays a vital role in modulating immune function and physiological homeostasis. In recent years, the Conserved Transcriptional Response to Adversity (CTRA) has emerged as a key marker of the body's response to chronic stress. This gene expression profile is characterized by SNS-mediated upregulation of pro-inflammatory genes (such as IL1B and TNF) and downregulation of antiviral response genes (e.g., IFI and MX families). CTRA has been observed in individuals exposed to prolonged stressors like loneliness, social isolation, and bereavement. Some research suggests that PNS activity, as indicated by heart rate variability (HRV), may help counteract the CTRA. However, previous PNS-CTRA studies have focused on Western populations, raising questions about the generalizability of these findings across different cultural and ethnic backgrounds. This study aimed to examine the relationship between HRV and CTRA gene expression in young, healthy adults in Japan. We hypothesized that HRV would be inversely related to CTRA gene expression, similar to patterns observed in previous Western studies. A total of 49 participants aged 20 to 39 were recruited, and after data exclusions, 26 participants' HRV and CTRA data were analyzed. HRV was measured using an electrocardiogram (ECG), and two time-domain indices were utilized: the root mean square of successive differences (RMSSD) and the standard deviation of NN intervals (SDNN). Blood samples were collected for gene expression analysis, focusing on a standard set of 47 CTRA indicator gene transcripts. it findings revealed a significant inverse relationship between HRV and CTRA gene expression, with higher HRV correlating with reduced pro-inflammatory gene activity and increased antiviral response. These results are consistent with findings from Western populations and demonstrate that the relationship between ANS function and immune response generalizes to an East Asian population. The study highlights the importance of HRV as a biomarker for psychophysiological health, reflecting the body's ability to buffer stress and maintain immune balance. These findings have implications for understanding how physiological systems interact across different cultures and ethnicities. Given the influence of chronic stress in promoting inflammation and disease risk, interventions aimed at improving HRV, such as mindfulness-based practices or physical exercise, could provide significant health benefits. Future research should focus on larger sample sizes and experimental interventions to better understand the causal pathways linking HRV to CTRA gene expression, and determine whether improving HRV may help mitigate the harmful effects of stress on health by reducing inflammation.

Keywords: autonomic nervous activity, neuroendocrine system, inflammation, Japan

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Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer

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To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.

Keywords: COVID19, epigenetics, DNA mathylation, viral infection

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Authors: Manav Sabharwal, Ruda Rai Md, Candace Parker, James Ridley

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Wheat is one of the most commonly consumed grains worldwide, which contains gluten. Nowadays, gluten intake is considered to be a trigger for GRDs, including Celiac disease (CD), a common genetic disease affecting 1% of the US population, non-celiac gluten sensitivity (NCGS) and wheat allergy. NCGS is being recognized as an acquired gluten-sensitive enteropathy that is prevalent across age, ethnic and geographic groups. The cause of this entity is not fully understood, and recent studies suggest that it is more common in participants with irritable bowel syndrome (IBS), with iron deficiency anemia, symptoms of fatigue, and has considerable overlap in symptoms with IBS and Crohn’s disease. However, these studies were lacking in availability of complete serologies, imaging tests and/or pan-endoscopy. We performed a prospective study of 745 adult patients who presented to an outpatient clinic for evaluation of chronic upper gastro-intestinal symptoms and subsequently underwent an upper endoscopic (EGD) examination as standard of care. Evaluation comprised of comprehensive celiac antibody panel, inflammatory bowel disease (IBD) serologic markers, duodenal biopsies and Small Bowel Video Capsule Endoscopy (VCE), when available. At least 6 biopsy specimens were obtained from the duodenum and proximal jejunum during EGD, and CD3+ Intraepithelial lymphocytes (IELs) and villous architecture were evaluated by a single experienced pathologist, and VCE was performed by a single experienced gastroenterologist. Of the 745 patients undergoing EGD, 12% (93/745) patients showed elevated CD3+ IELs in the duodenal biopsies. 52% (387/745) completed a comprehensive CD panel and 7.2% (28/387) were positive for at least 1 CD antibody (Tissue transglutaminase (tTG), being the most common antibody in 65% (18/28)). Of these patients, 18% (5/28) showed increased duodenal CD3+ IELs, but 0% showed villous blunting or distortion to meet criteria for CD. Surprisingly, 43% (12/28) were positive for at 1 IBD serology (ASCA, ANCA or expanded IBD panel (LabCorp)). Of these 28 patients, 29% (8/28) underwent a SB VCE, of which 100 % (8/8) showed significant jejuno-ileal mucosal lesions diagnostic for IBD. Findings of abnormal CD antibodies (7.2%, 28/387) and increased CD3+ IELs on duodenal biopsy (12%, 93/745) were observed frequently in patients with UGI symptoms undergoing EGD in an outpatient clinic. None met criteria for CD, and a high proportion (43%, 12/28) showed evidence of overlap with IBD. This suggests a potential causal link of acquired GRDs to underlying inflammation and gut mucosal barrier disruption. Further studies to investigate a role for abnormal antigen presentation of dietary gluten to gut associated lymphoid tissue as a cause are justified. This may explain a high prevalence of GRDs in the population and correlation with IBS, IBD and other gut inflammatory disorders.

Keywords: celiac, gluten sensitive enteropathy, lymphocitic enteritis, IBS, IBD

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Authors: Neda Valizadeh, Soudabeh Shafiee Ardestani, Arvin Najafi

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Objectives: The aim of this study is to evaluate the association of mid-regional pro-atrial natriuretic peptide (MRproANP), procalcitonin (PCT), proendothelin-1 (proET-1) levels with sepsis severity in Emergency ward patients. Materials and Methods: We assessed the predictive value of MRproANP, PCT, copeptin, and proET-1 in early sepsis among patients referring to the emergency ward with a suspected sepsis. Results-132 patients were enrolled in this study. 45 (34%) patients had a final diagnosis of sepsis. A higher percentage of patients with definite sepsis had systemic inflammatory response syndrome (SIRS) criteria at initial visit in comparison with no-sepsis patients (P<0.05) and were admitted to the hospital (P<0.05). PCT levels were higher in sepsis patients [P<0.05]. There was no significant differences for MRproANP or proET-1 in sepsis patients (P=0.47). Conclusion: A combination of SIRS criteria and PCT levels is beneficial for the early sepsis diagnosis in emergency ward patients with a suspicious infection disease.

Keywords: emergency, prolactin, sepsis, biomarkers

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Authors: Ammar Ouahab, Meriem Houichi , Sanna Mihoubi

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Background: Nigella sativa is an annual flowering plant, belongs to the Ranunculaceae family. It has many pharmacological activities such as anti-inflammatory; anti-bacterial; anti-hepatotoxic activities etc. Materials: In order to predict the pharmacological activity of Nigella Sativa’s compounds, some web based servers were used, namely, PubChem, Molinspiration, ADMET-SAR, PASS online and PharMapper. In addition to that, AutoDOCK was used to investigate the different molecular interactions between the selected compounds and their target proteins. Results: All compounds displayed a stable interaction with their targets and satisfactory binding energies, which means that they are active on their targets. Conclusion: Nigella sativa is an effective medicinal plant that has several ethno-medical uses; the latter uses are proven herein via an in-silico study of their pharmacological activities.

Keywords: Nigella sativa, AutoDOCK, PubChem, Molinspiration, ADMET-SAR, PharMapper, PASS online server, docking

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Authors: Chaoran Liu

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Bioactive polysaccharides and polysaccharide-protein complex derived from mushrooms and fungi have a wide range of immunomodulatory activity with low side-effects and have therefore the potential to be developed as an adjuvant in cancer therapies. Mushrooms sclerotium is rich in polysaccharides and the polysaccharides isolated from the sclerotium of Polyporus rhinocerus have shown potent in vivo and in vitro immunomodulatory effects. Macrophages are considered to be an important component of the innate immune response against bacterial infection and cancer. To better understanding the immunomodulatory effects and its underlying mechanisms of sclerotial water-soluble polysaccharides extracted from P. rhinocerus on macrophages, the objectives of this study are to purify the water-soluble novel sclerotial polysaccharides and to characterize the structure and properties as well as to study the detailed molecular mechanisms of the in vitro immunomodulating effects in murine macrophages. The hot water-soluble fraction PRW from the sclerotium of P. rhinocerus was obtained using solvent extraction. PRW was further fractionated by membrane ultrafiltration to a give a fraction (PRW1) with molecular mass less than 50 kDa. PRW1 was characterized to be a polysaccharide-protein complex composed of 45.7% polysaccharide and 44.2% protein. The chemical structure of the carbohydrate moiety of PRW1 was elucidated by GC and FTIR to be mainly beta-D-glucan with trace amount of galactose and mannose. The immunomodulatory effects of PRW1 on murine RAW 264.7 macrophages were demonstrated in terms of the increase in nitric oxide production and cytokine production. Mechanistically, PRW1 initiates ERK phosphorylation to activate macrophages within 15 min and significantly improves the expression level of inducible NOS (iNOS) from 6 h after treatment. In summary, this study indicates that PRW1 is a potent immunomodulatory agent for macrophages and suggests that mushroom sclerotia from Polyporus rhinocerus requires for further investigation in cancer research.

Keywords: Polyporus rhinocerus, mushroom sclerotia, Polysaccharide-Protein Complex, macrophage activation

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Authors: Jie Lin, Yiwen Pan, Li Zhang, Zhangyong Xia

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Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and extracellular matrix in the arterial walls. This pathological process can lead to the formation of plaques that can obstruct blood flow and trigger various cardiovascular diseases such as heart attack and stroke. The underlying molecular mechanisms still remain unclear, although many studies revealed the dysfunction of endothelial cells, recruitment and activation of monocytes and macrophages, and the production of pro-inflammatory cytokines and chemokines in atherosclerosis. This study aimed to identify hub genes involved in the progression of atherosclerosis and to analyze their biological function in silico, thereby enhancing our understanding of the disease’s molecular mechanisms. Through the analysis of microarray data, we examined the gene expression in media and neo-intima from plaques, as well as distant macroscopically intact tissue, across a cohort of 32 hypertensive patients. Initially, 112 differentially expressed genes (DEGs) were identified. Subsequent immune infiltration analysis indicated a predominant presence of 27 immune cell types in the atherosclerosis group, particularly noting an increase in monocytes and macrophages. In the Weighted gene co-expression network analysis (WGCNA), 10 modules with a minimum of 30 genes were defined as key modules, with blue, dark, Oliver green and sky-blue modules being the most significant. These modules corresponded respectively to monocyte, activated B cell, and activated CD4 T cell gene patterns, revealing a strong morphological-genetic correlation. From these three gene patterns (modules morphology), a total of 2509 key genes (Gene Significance >0.2, module membership>0.8) were extracted. Six hub genes (CD36, DPP4, HMOX1, PLA2G7, PLN2, and ACADL) were then identified by intersecting 2509 key genes, 102 DEGs with lipid-related genes from the Genecard database. The bio-functional analysis of six hub genes was estimated by a robust classifier with an area under the curve (AUC) of 0.873 in the ROC plot, indicating excellent efficacy in differentiating between the disease and control group. Moreover, PCA visualization demonstrated clear separation between the groups based on these six hub genes, suggesting their potential utility as classification features in predictive models. Protein-protein interaction (PPI) analysis highlighted DPP4 as the most interconnected gene. Within the constructed key gene-drug network, 462 drugs were predicted, with ursodeoxycholic acid (UDCA) being identified as a potential therapeutic agent for modulating DPP4 expression. In summary, our study identified critical hub genes implicated in the progression of atherosclerosis through comprehensive bioinformatic analyses. These findings not only advance our understanding of the disease but also pave the way for applying similar analytical frameworks and predictive models to other diseases, thereby broadening the potential for clinical applications and therapeutic discoveries.

Keywords: atherosclerosis, hub genes, drug prediction, bioinformatics

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Authors: Hossein Mostafavi

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A diversity of biological activities and pharmaceutical uses have been attributed to gallic acid derivatives such as antibacterial, anticancer, anti inflammatory. A series of gallic acid derivatives were synthesized, and their structure was confirmed by FT-IR, HNMR, CNMR, elemental analysis. In vitro biological activity of compounds was determined against Proteus vulgaris ATCC 7829, Escherichia coli ATCC 25922, as (Gram-negative) bacteria and bacillus cereus ATCC 11778, Staphylococus aureus ATCC 6538 as (Gram-positive) bacteria. Antibacterial susceptibility tests were done by use of the paper disc diffusion method on Mueller Hinton agar (Merck). Chloramiphenicol, Penicilline, Streptomycin and Tetracycline were standard reference antibiotics. The zone of inhibition against bacteria was measured after 24 hours at 37 °C. Compounds 3, 4, 5 were the main antibacterial compounds against Gram-negative bacteria but not Gram-positive.

Keywords: gallic acid derivatives, antibacterial, antibiotics, inhibition

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Authors: Anita Bajpai, Sarah Duan, Ashlee Erskine, Shehzein Khan, Raymond Kramer

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Introduction: This research focuses on exploring the beneficial effects if any, of Vitamin-D in reducing the need for supplemental oxygen among hospitalized COVID-19 patients. Two questions are investigated – Q1)Doeshaving a healthy level of baselineVitamin-D 25-OH (≥ 30ng/ml) help,andQ2) does administering Vitamin-D therapy after-the-factduring inpatient hospitalization help? Methods/Study Design: This is a comprehensive, retrospective, observational study of all inpatients at RUHS from March through December 2020 who tested positive for COVID-19 based on real-time reverse transcriptase–polymerase chain reaction assay of nasal and pharyngeal swabs and rapid assay antigen test. To address Q1, we looked atall N1=182 patients whose baseline plasma Vitamin-D 25-OH was known and who needed supplemental oxygen. Of this, a total of 121 patients had a healthy Vitamin-D level of ≥30 ng/mlwhile the remaining 61 patients had low or borderline (≤ 29.9ng/ml)level. Similarly, for Q2, we looked at a total of N2=893 patients who were given supplemental oxygen, of which713 were not given Vitamin-D and 180 were given Vitamin-D therapy. The numerical value of the maximum amount of oxygen flow rate(dependent variable) administered was recorded for each patient. The mean values and associated standard deviations for each group were calculated. Thesetwo sets of independent data served as the basis for independent, two-sample t-Test statistical analysis. To be accommodative of any reasonable benefitof Vitamin-D, ap-value of 0.10(α< 10%) was set as the cutoff point for statistical significance. Results: Given the large sample sizes, the calculated statistical power for both our studies exceeded the customary norm of 80% or better (β< 0.2). For Q1, the mean value for maximumoxygen flow rate for the group with healthybaseline level of Vitamin-D was 8.6 L/min vs.12.6L/min for those with low or borderline levels, yielding a p-value of 0.07 (p < 0.10) with the conclusion that those with a healthy level of baseline Vitamin-D needed statistically significant lower levels of supplemental oxygen. ForQ2, the mean value for a maximum oxygen flow rate for those not administered Vitamin-Dwas 12.5 L/min vs.12.8L/min for those given Vitamin-D, yielding a p-valueof 0.87 (p > 0.10). We thereforeconcludedthat there was no statistically significant difference in the use of oxygen therapy between those who were or were not administered Vitamin-D after-the-fact in the hospital. Discussion/Conclusion: We found that patients who had healthy levels of Vitamin-D at baseline needed statistically significant lower levels of supplemental oxygen. Vitamin-D is well documented, including in a recent article in the Lancet, for its anti-inflammatory role as an adjuvant in the regulation of cytokines and immune cells. Interestingly, we found no statistically significant advantage for giving Vitamin-D to hospitalized patients. It may be a case of “too little too late”. A randomized clinical trial reported in JAMA also did not find any reduction in hospital stay of patients given Vitamin-D. Such conclusions come with a caveat that any delayed marginal benefits may not have materialized promptly in the presence of a significant inflammatory condition. Since Vitamin-D is a low-cost, low-risk option, it may still be useful on an inpatient basis until more definitive findings are established.

Keywords: COVID-19, vitamin-D, supplemental oxygen, vitamin-D in primary care

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Authors: Tristan R. Fraser, Christopher D. Steadman, Christopher J. Boos

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Myopericarditis is an inflammation syndrome characterised by clinical diagnostic criteria for pericarditis, such as chest pain, combined with evidence of myocardial involvement, such as elevation of biomarkers of myocardial damage, e.g., troponins. It can rarely be a complication of therapeutics used for dysregulated immune-mediated diseases such as inflammatory bowel disease (IBD), for example, mesalazine. The infrequency of mesalazine-induced myopericarditis adds to the challenge in its recognition. Rapid diagnosis and the early introduction of treatment are crucial. This case report follows a 24-year-old professional footballer with a past medical history of ulcerative colitis, recently started on mesalazine for disease control. Three weeks after mesalazine was initiated, he was admitted with fever, shortness of breath, and chest pain worse whilst supine and on deep inspiration, as well as elevated venous blood cardiac troponin T level (cTnT, 288ng/L; normal: <13ng/L). Myocarditis was confirmed on initial inpatient cardiac MRI, revealing the presence of florid myocarditis with preserved left ventricular systolic function and an ejection fraction of 67%. This was a longitudinal case study following the progress of a single individual with myopericarditis over four acute hospital admissions over nine weeks, with admissions ranging from two to five days. Parameters examined included clinical signs and symptoms, serum troponin, transthoracic echocardiogram, and cardiac MRI. Serial measurements of cardiac function, including cardiac MRI and transthoracic echocardiogram, showed progressive deterioration of cardiac function whilst mesalazine was continued. Prior to cessation of mesalazine, transthoracic echocardiography revealed a small global pericardial effusion of < 1cm and worsening left ventricular systolic function with an ejection fraction of 45%. After recognition of mesalazine as a potential cause and consequent cessation of the drug, symptoms resolved, with cardiac MRI performed as an outpatient showing resolution of myocardial oedema. The patient plans to make a return to competitive sport. Patients suffering from myopericarditis are advised to refrain from competitive sport for at least six months in order to reduce the risk of cardiac remodelling and sudden cardiac death. Additional considerations must be taken in individuals for whom competitive sport is an essential component of their livelihood, such as professional athletes. Myopericarditis is an uncommon, however potentially serious medical condition with a wide variety of aetiologies, including viral, autoimmune, and drug-related causes. Management is mainly supportive and relies on prompt recognition and removal of the aetiological process. Mesalazine-induced myopericarditis is a rare condition; as such increasing awareness of mesalazine as a precipitant of myopericarditis is vital for optimising the management of these patients.

Keywords: myopericarditis, mesalazine, inflammatory bowel disease, professional athlete

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Authors: Katherine Madero Valencia, Carlos Jaramillo, Elida Dueñas, Carlos Torres, María Del Pilar Delgado

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Asthma, described as a chronic inflammatory condition of the airways, courses accompanied by episodes known as exacerbations, characterized by a worsening of symptoms. Among the triggers, some allergen-irritative and infectious agents are found, including Chlamydophila pneumoniae which seems to play an increasingly important role. In this paper a PCR was used to detect C. pneumoniae in order to estimate the frequency of infections caused by this agent in pediatric patients with asthma exacerbations. C. pneumoniae distribution throughout the study period was also evaluated. 175 nasopharyngeal aspirates from children with asthma exacerbations were analyzed by PCR and sequencing. A global prevalence of C. pneumoniae of 53.71% was obtained. This study highlights a high circulation of C. pneumoniae during the study period, in children of all ages and especially in children under 5 years old. Molecular tests applied permit a rapid detection and improved our knowledge about these infections in children with asthma.

Keywords: Chlamydophila pneumoniae, detection, molecular techniques, pediatric asthma

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Authors: Ann Ying-An Chen, Yi-Lun Tsai, Hso-Chi Chaung

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An understanding of pathogens and the immune system has played an utmost important role in agricultural research for the development of vaccinations. The immunological synapse, cell to cell interaction play a crucial role in triggering the body's immune system, such as activation between antigen-presenting cells (APCs) and different subsets of T-cell. If these interactions are regulated appropriately, the host has the ability to defend itself against a wide spectrum of infectious pathogens. The aim of this study is to establish and to characterize a porcine immune synapse system by co-culturing T cell/APC. In this study, blood samples were collected from specific-pathogen-free piglets, and peripheral blood mononuclear cells (PBMC) were separated by using Ficoll-Pague. The PBMC were then stained with CD4 (FITC) and CD25 (PE) antibodies. Different subsets of T cells sorted by fluorescence-activated cell sorting flow cytometer were co-cultured for 24 hrs with alveolar macrophages, and the profiles of cytokine secretion and mRNA transcription levels of Toll-like receptors were examined after. Results showed that the three stages of immune synapse were clearly visible and identified under both transmission and scanning electron microscope (TEM and SEM). The significant interaction differences in toll-like receptor expressions within the co-cultured cell system were observed. The TLR7 mRNA expressions in CD4+CD25- cells were lower than those in CD4+CD25+ and CD4 -CD25+. Interestingly, the IL-10 production levels in CD4+CD25- cells (7.732 pg/mL) were significantly higher than those of CD4+CD25+ (2.636 pg/mL) and CD4 -CD25+ (2.48 pg/mL). These findings demonstrated that a clear understanding of the porcine immune synapse system can contribute greatly for further investigations on the mechanism of T-cell activation, which can benefit in the discovery of potential adjuvant candidate or effective antigen epitopes in the development of vaccinations with high efficacy.

Keywords: antigen-presenting cells, immune synapse, pig, T subsets, toll-like receptor

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Authors: Sudip Ghosh, Dipanwita Roy, Dipan Chatterjee, Paramita Bhattacharjee, Satadal Das

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Highest yield of eugenol-rich fractions from Cinnamomum tamala (bay leaf) leaves were obtained by supercritical carbon dioxide (SC-CO2), compared to hydro-distillation, organic solvents, liquid CO2 and subcritical CO2 extractions. Optimization of SC-CO2 extraction parameters was carried out to obtain an extract with maximum eugenol content. This was achieved using a sample size of 10 g at 55°C, 512 bar after 60 min at a flow rate of 25.0 cm3/sof gaseous CO2. This extract has the best combination of phytochemical properties such as phenolic content (1.77 mg gallic acid/g dry bay leaf), reducing power (0.80 mg BHT/g dry bay leaf), antioxidant activity (IC50 of 0.20 mg/ml) and anti-inflammatory potency (IC50 of 1.89 mg/ml). Identification of compounds in this extract was performed by GC-MS analysis and its antimicrobial potency was also evaluated. The MIC values against E. coli, P. aeruginosa and S. aureus were 0.5, 0.25 and 0.5 mg/ml, respectively.

Keywords: antimicrobial potency, Cinnamomum tamala, eugenol, supercritical carbon dioxide extraction

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Authors: Dalila Bouamra, Chekib Arslane Baki, Abdelhamid Bouchebour, Fatiha Koussa, Amel Benamara, Seoussen Kada

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The activity of methanolic extract from Anacyclus pyrethrum was evaluated using λ-carrageenan 1% induced paw edema in Wistar Albinos rats. The oral administration of 200 mg/kg, 400 mg/kg and 600 mg/kg, body weight of methanolic extract, one hour before induction of inflammation, exerted a significant inhibition effect of 47%, 57% and 62% respectively after 4h λ-carrageenan treatment and highly significant inhibition effect of 57%, 66% and 75% respectively after 8h λ-carrageenan treatment, compared to non treated group (100%) and that treated with aspirin, a standard anti-inflammatory drug. On the other hand, the effect of the plant extract on stomach was macroscopically and microscopically studied. The plant extract has an impact on the loss ratio of granulocytes that have invaded the stomach after a period of inflammation at a dose of 600 mg/kg body weight.

Keywords: inflammation, Anacyclus pyrethrum, gastritis, Wistar Albinos rats

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Authors: Azza A. Ali, Abeer I. Abd El-Fattah, Shaimaa S. Hussein, Hanan A. Abd El-Samea, Karema Abu-Elfotuh

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Background: Aluminium (Al) represents an environmental risk factor. Exposure to high levels of Al causes neurotoxic effects and different diseases. Vinpocetine is widely used to improve cognitive functions, it possesses memory-protective and memory-enhancing properties and has the ability to increase cerebral blood flow and glucose uptake. Cocoa bean represents a rich source of iron as well as a potent antioxidant. It can protect from the impact of free radicals, reduces stress as well as depression and promotes better memory and concentration. Wheatgrass is primarily used as a concentrated source of nutrients. It contains vitamins, minerals, carbohydrates, amino acids and possesses antioxidant and anti-inflammatory activities. Coenzyme Q10 (CoQ10) is an intracellular antioxidant and mitochondrial membrane stabilizer. It is effective in improving cognitive disorders and has been used as anti-aging. Zinc is a structural element of many proteins and signaling messenger that is released by neural activity at many central excitatory synapses. Objective: To study the role of some nutrients and drugs as Vinpocetine, Cocoa, Wheatgrass, CoQ10 and Zinc against neurotoxicity induced by Al in rats as well as to compare between their potency in providing protection. Methods: Seven groups of rats were used and received daily for three weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except for the control group which received saline. All groups of Al-toxicity model except one group (non-treated) were co-administered orally together with AlCl3 the following treatments; Vinpocetine (20mg/kg), Cocoa powder (24mg/kg), Wheat grass (100mg/kg), CoQ10 (200mg/kg) or Zinc (32mg/kg). Biochemical changes in the rat brain as acetyl cholinesterase (ACHE), Aβ, brain derived neurotrophic factor (BDNF), inflammatory mediators (TNF-α, IL-1β), oxidative parameters (MDA, SOD, TAC) were estimated for all groups besides histopathological examinations in different brain regions. Results: Neurotoxicity and neurodegenerations in the rat brain after three weeks of Al exposure were indicated by the significant increase in Aβ, ACHE, MDA, TNF-α, IL-1β, DNA fragmentation together with the significant decrease in SOD, TAC, BDNF and confirmed by the histopathological changes in the brain. On the other hand, co-administration of each of Vinpocetine, Cocoa, Wheatgrass, CoQ10 or Zinc together with AlCl3 provided protection against hazards of neurotoxicity and neurodegenerations induced by Al, their protection were indicated by the decrease in Aβ, ACHE, MDA, TNF-α, IL-1β, DNA fragmentation together with the increase in SOD, TAC, BDNF and confirmed by the histopathological examinations of different brain regions. Vinpocetine and Cocoa showed the most pronounced protection while Zinc provided the least protective effects than the other used nutrients and drugs. Conclusion: Different degrees of protection from neurotoxicity and neuronal degenerations induced by Al could be achieved through the co-administration of some nutrients and drugs during its exposure. Vinpocetine and Cocoa provided the most protection than Wheat grass, CoQ10 or Zinc which showed the least protective effects.

Keywords: aluminum, neurotoxicity, vinpocetine, cocoa, wheat grass, coenzyme Q10, Zinc, rats

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Authors: M. Rajasekar, K. Suresh

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Diosmin is a flavonoid, most abundantly found in many citrus fruits. As a flavonoid, it possesses a multitude of biological activities including anti-hyperglycemic, anti-lipid peroxidative, anti-inflammatory, antioxidant, and anti-mutagenic properties. At this point, we established the anti-proliferative and apoptosis-inducing activities of diosmin in Hep-2 and KB cells. Diosmin has cytotoxic effects through inhibiting cellular proliferation of Hep-2 and KB cells, which leads to the induction of apoptosis, as apparent by an increase in the fraction of cells in the sub-G1phase of the cell cycle. Results exposed that inhibition of cell proliferation is associated with regulation of the Interleukins/STAT pathway. In addition, Diosmin treatment with Hep-2 and KB cells actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. And also an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade and shifting the balance in favor of apoptosis. These observations conclude that Diosmin induce apoptosis via Interleukins /STAT-mediated pathway.

Keywords: diosmin, apoptosis, antioxidant, STAT pathway

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Authors: Azza A. Ali, Mona G. Khalil, Hemat A. Elariny, Shereen S. El Shaer

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Background: Aluminium (Al) is very abundant metal in the earth’s crust. It is a constituent of cooking utensils, medicines, cosmetics, some foods and food additives. Salts of Al are widely used in the treatment of drinking water for purification purposes. Excessive and prolonged exposure to Al causes oxidative stress and impairment of many physiological functions. Its accumulation in liver and kidney causes hepatotoxicity and nephrotoxicity. Social isolation (SI) or Protein malnutrition (PM) also increases oxidative stress and may enhance the toxicity of Al as well as the degeneration in liver and kidney. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has strong antioxidant as well as anti-inflammatory activities and can protect against oxidative stress-induced degenerations. Objective: To study the influence of stress or PM on Al-induced nephrotoxicity and hepatotoxicity in rats, as well as on the potential role of EGCG in providing protection. Methods: Rats received daily AlCl3 (70 mg/kg, IP) for three weeks (Al-toxicity groups) except one normal control group received saline. Al-toxicity groups were divided into four treated and four untreated groups; treated rats received EGCG (10 mg/kg, IP) together with AlCl3. One group of both treated and untreated rats served as control for each of them, and the others were subjected to either stress (mild using isolation or high using electric shock) or to PM (10% casein diet). Specimens of liver and kidney were used for assessment of levels of inflammatory mediators as TNF-α, IL6β, nuclear factor kappa B (NF-κB), oxidative stress (MDA, SOD, TAC, NO), Caspase-3 and for DNA fragmentation as well as for histopathological examinations. Biochemical changes were also measured in the serum as total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea as well as the level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate deshydrogenase (LDH). Results: Nephrotoxicity and hepatotoxicity induced by Al were enhanced in rats exposed to stress and to PM. The influence of stress was more pronounced than PM. Al-toxicity was indicated by the increase in liver and kidney MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3, DNA fragmentation and in ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea levels, together with the decrease in total proteins, SOD, TAC. EGCG provided protection against hazards of Al as indicated by the decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation as well as in levels of ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea in liver and kidney, together with the increase in total proteins, SOD, TAC and confirmed by histopathological examinations. It provided more pronounced protection in high stressful conditions than in mild one than in PM. Conclusion: Stress have a bad impact on Al-induced nephrotoxicity and hepatotoxicity more than PM. Thus it can clarify and maximize the role of EGCG in providing protection. Consequently, administration of EGCG is advised with excessive Al-exposure to avoid nephrotoxicity and hepatotoxicity especially in populations more subjected to stress or PM.

Keywords: aluminum, stress, protein malnutrition, nephrotoxicity, hepatotoxicity, epigallocatechin-3-gallate, rats

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Authors: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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Authors: Megan L. Srinivas

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Individuals with underlying rheumatologic diseases such as dermatomyositis may not adequately respond to tuberculin (PPD) skin tests, creating false negative results. These illnesses are frequently treated with immunosuppressive therapy making proper identification of TB infection imperative. A 59-year-old Filipino man was diagnosed with dermatomyositis on the basis of rash, electromyography, and muscle biopsy. He was initially treated with IVIG infusions and transitioned to oral prednisone and mycophenolate. The patient’s symptoms improved on this regimen. Six months after starting mycophenolate, the patient began having fevers, night sweats, and productive cough without hemoptysis. He moved from the Philippines 5 years prior to dermatomyositis diagnosis, denied sick contacts, and was PPD negative both at immigration and immediately prior to starting mycophenolate treatment. A third PPD was negative following the onset of these new symptoms. He was treated for community-acquired pneumonia, but symptoms worsened over 10 days and he developed watery diarrhea and a growing non-tender, non-mobile mass on the left side of his neck. A chest x-ray demonstrated a cavitary lesion in right upper lobe suspicious for TB that had not been present one month earlier. Chest CT corroborated this finding also exhibiting necrotic hilar and paratracheal lymphadenopathy. Neck CT demonstrated the left-sided mass as cervical chain lymphadenopathy. Expectorated sputum and stool samples contained acid-fast bacilli (AFB), cultures showing TB bacteria. Fine-needle biopsy of the neck mass (scrofula) also exhibited AFB. An MRI brain showed nodular enhancement suspected to be a tuberculoma. Mycophenolate was discontinued and dermatomyositis treatment was switched to oral prednisone with a 3-day course of IVIG. The patient’s infection showed sensitivity to standard RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) treatment. Within a week of starting RIPE, the patient’s diarrhea subsided, scrofula diminished, and symptoms significantly improved. By the end of treatment week 3, the patient’s sputum no longer contained AFB; he was removed from isolation, and was discharged to continue RIPE at home. He was discharged on oral prednisone, which effectively addressed his dermatomyositis. This case illustrates the unreliability of PPD tests in patients with long-term inflammatory diseases such as dermatomyositis. Other immunosuppressive therapies (adalimumab, etanercept, and infliximab) have been affiliated with conversion of latent TB to disseminated TB. Mycophenolate is another immunosuppressive agent with similar mechanistic properties. Thus, it is imperative that patients with long-term inflammatory diseases and high-risk TB factors initiating immunosuppressive therapy receive a TB blood test (such as a quantiferon gold assay) prior to the initiation of therapy to ensure that latent TB is unmasked before it can evolve into a disseminated form of the disease.

Keywords: dermatomyositis, immunosuppressant medications, mycophenolate, disseminated tuberculosis

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Authors: Maryam Hamedanlou, Shahla Hajializadeh

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The transdermal drug delivery system is one of the types of novel drug delivery system that the drug is absorbed into the skin. The major considerations for designing and producing transdermal patch are small size, suitable drug release and good adhering. In this study, drug-in-adhesive transdermal patch contained non-steroidal anti-inflammatory ketoprofen is prepared. Also, the effect of non-woven fabric and plastic backing layers on adhesion properties is assessed. The results of the test, demonstrated the use of plastic backing layer increases tack and peel rather than non-woven fabric type. The balance tack with plastic backing layer patch is 6.7 (N/mm2), and the fabric one is 3.8 (N/mm2), and their peel is 9.2 (N/25mm) and 8.3 (N/25mm) by arrangement.

Keywords: transdermal drug delivery system, single layer patch of ketoprofen, plastic layer, fabric backing layer

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Authors: Mohamed El Moctar Abeidi

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The indazole derivatives exhibit a wide spectrum of biological activities. They are known for their anti-tumor, antiplatelet, anti-viral, anti-microbial, anti-inflammatory, anti-leishmania and even anti-spermatogen. As part of our research on the synthesis of a number of heterocycles capable of exhibiting a biological and pharmacological property, due to our ongoing interest in the development of a simple and low-cost procedure for obtaining heterocyclic compounds that may have an interest for medicinal purposes. We present in this work the synthesis of 6-nitro-indazoles derivatives, using two different methods. the first method is the alkylation of Nitroindazole by two different alkylating agents under the conditions of solid/liquid phase transfer catalysis in N, N-dimethylformamide (DMF) in the presence of potassium carbonate (K₂CO₃) as a base, and tetra-n-butylammonium bromide (BTBA) as a catalyst. While the other method is the 1,3-dipolar cycloaddition, in this case, we have undertaken the preparation of bi-heterocyclic containing the 6-nitroindazole associate with group of isoxazoline, isoxazole or 1,2,3-Triazole under normal conditions and, under the catalytic conditions of the click chemistry we were also able to determine the structures without any ambiguity by the ¹H and ¹³C NMR.

Keywords: indazole, 6-nitroindazole, isoxazole, 1, 2, 3-Triazole

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Authors: Deepak Mohan, Sushma Sharma

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Diclofenac sodium, a member of the acetic acid family of non-steroidal anti-inflammatory drugs, is used to retard inflammation, arthritis pain and ankylosing spondylitis. The drug is known to cause severe injury in different tissues due to formation of reactive oxygen species. The present study is focused on the effect of different doses of diclofenac (4 mg/kg/body weight and 14 mg/kg/body weight on histoarchitecture of the liver from 7-28 days of the investigation. Diclofenac administration resulted in distorted hepatic degeneration and formation of wide areas in the form of sinusoidal gaps. Hepatic fibrosis noticed in different stages of investigation could be attributed to chronic inflammation and reactive oxygen species which results in deposition of extracellular matrix proteins. The abrupt degenerative changes observed during later stages of the experiment showed maximum damage to the liver, and there was enlargement of sinusoidal gaps accompanied by maximum necrosis in the tissues.

Keywords: arthritis, diclofenac, histoarchitecture, sinusoidal

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Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

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Authors: Ali Asghar Saki, Sayed Ali Hosseini Siyar, Abbass Ashoori

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This study was conducted to evaluate the effect of Echinacea purpurea on the expression of cyclooxygenase-2 (COX-2), interleukin-17F (IL-17F) in seven-day-old broiler chickens. Four groups were fed with concentration of 0 g/kg, 5 g/kg, 10 g/kg and 20 g/kg from the root of E. purpurea in the basal diet and two other groups were only fed with the basal diet for 21 days. At the 28^th day, lipopolysaccharide (LPS, 2 mg/kg diet) was injected in four groups and the basal diet group was injected by saline as control. The chickens’ spleen RNA expression was measured for the COX-2 and IL-17F genes by Real-Time PCR. The results have shown that chickens which were fed E. purpurea had a lower COX-2 and IL-17F mRNA expression. The chickens who have received LPS only, lymphocyte was lower than other treatments. Vital organ weights were not significantly different, but body weight loss was recovered by dietary herbs inclusion. The results of this study have shown the positive effect of an anti-inflammatory herb to prevent the undesirable effect of inflammation.

Keywords: broiler chickens, Echinacea purporea, gene expression, lipopolysaccharide

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