Search results for: cardiac inflammation

Authors: Pei-Hsiu Chiang, Ling Hong Huang, Hsin-I Chang

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In this research, we used UVA irradiation, which can penetrate into dermis and fibroblasts, the most abundant cells in dermis, to investigate the effect of UV light on dermis, such as inflammation, ECM degradation and elasticity loss. Moreover, this research is focused on the influence of hyaluronic acid (HA) on UVA treated dermal fibroblasts. We aim to establish whether HA can effectively relief ECM degradation, and restore the elasticity of UVA-damaged fibroblasts. Prolonged exposure to UVA radiation can damage fibroblasts and led variation in cell morphology and reduction in cell viability. Besides, UVA radiation can induce IL-1β expression on fibroblasts and then promote MMP-1 and MMP-3 expression, which can accelerate ECM degradation. On the other hand, prolonged exposure to UVA radiation reduced collagen and elastin synthesis on fibroblasts. Due to the acceleration of ECM degradation and the reduction of ECM synthesis, Atomic force microscope (AFM) was used to analyze the elasticity reduction on UVA-damaged fibroblasts. UVA irradiation causes photoaging on fibroblasts. UVA damaged fibroblasts with HA treatment can down-regulate the gene expression of MMP-1, MMP-3, and then slow down ECM degradation. On the other hand, HA may restore elastin and collagen synthesis in UV-damaged fibroblasts. Based on the slowdown of ECM degradation, UVA-damaged fibroblast elasticity can be effectively restored by HA treatment. In summary, HA can relief the photoaging conditions on fibroblasts, but may not be able to return fibroblasts to normal, healthy state. Although HA cannot fully recover UVA-damaged fibroblasts, HA is still potential for repairing photoaging skin.

Keywords: atomic force microscope, hyaluronic acid, UVA radiation, dermal fibroblasts

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Authors: Nabil Ghedadba, Abdessemed Samira, Leila Hambaba, Sidi Mohamed Ould Mokhtar, Nassima Fercha, Houas Bousselsela

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The overall objective of this study was to evaluate in vitro the hemostatic activity of secondary metabolites (polyphenols, flavonoids, and tannins) of Marrubium vulgare leaves, aromatic plant widely used in traditional medicine for the treatment of asthma, cough, diabetes (by its effect on the pancreas to secrete insulin), heart disease, fever has a high efficiency as against inflammation. Qualitative analysis of the aqueous extract (AQE) by thin layer chromatography revealed the presence of quercetin, kaempferol and rutin. Quantification of total phenols by Folin Ciocalteu method and flavonoids by AlCl3 method gave high values with AQE: 175±0.80 mg GAE per 100g of the dry matter, 23.86±0.36 mg QE per 100g of dry matter. Moreover, the assay of condensed tannins by the vanillin method showed that AQE contains the highest value: 16.55±0.03 mg e-catechin per 100 g of dry matter. Assessment of hemostatic activity by the plasma recalcification method (time of Howell) has allowed us to discover the surprising dose dependent anticoagulant effect of AQE lyophilized from leaves of M. vulgare. A positive linear correlation between the two parameters studied: the content of condensed tannins and hemostatic activity (r=0.96) were used to highlight a possible role of these compounds that are potent vasoconstrictor activity in hemostatic. From these results we can see that Marrubium vulgre could be used for the treatment of health.

Keywords: Marrubium vulgare L., aqueous extract, phenolic compounds dosing, hemostatic activity, condensed tannins

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Authors: Fatin H. Mohamad, Jia H. Wong, Muhammad Bilal, Abdul A. Mohamed Yusoff, Jafri M. Abdullah, Jingli Zhang

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Kv1.4 is a Shaker-related member of voltage-gated potassium channel which can be associated with cardiac action potential but can also be found in Schaffer collateral and dentate gyrus. It has two inactivation mechanisms; the fast N-type and slow C-type. Kv1.4 produces rapid current inactivation. This A type potential of Kv1.4 makes it as a target in antiepileptic drugs (AEDs) selection. In this study, 4-hydroxybenzoic acid, which can be naturally found in bamboo shoots, were tested on its enhancement effect on potassium current of Kv1.4 channel expressed in Xenopus laevis oocytes using the two-microelectrode voltage clamp method. Current obtained were recorded and analyzed with pClamp software whereas statistical analysis were done by student t-test. The ratio of final / peak amplitude is an index of the activity of the Kv1.4 channel. The less the ratio, the greater the function of Kv1.4. The decrease of ratio of which by 1µM 4-hydroxybenzoic acid (n= 7), compared with 0.1% DMSO (vehicle), was mean= 47.62%, SE= 13.76%, P= 0.026 (statistically significant). It indicated more opening of Kv1.4 channels under 4-hydroxybenzoic acid. In conclusion, 4-hydroxybenzoic acid can enhance the function of Kv1.4 potassium channels, which is regarded as one of the mechanisms of antiepileptic treatment.

Keywords: antiepileptic, Kv1.4 potassium channel, two-microelectrode voltage clamp, Xenopus laevis oocytes, 4-hydroxybenzoic acid

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Authors: Adriana B. Ribeiro, Camila B. Araujo, Frank L. Bueno, Luiz Eduardo V. Silva, Caroline V. Fortes, Helio C. Salgado, Rubens Fazan Jr., Claudia H. L. da Silva

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Denture-related stomatitis (DRS) has recently been associated with deleterious cardiovascular effects, including hypertension. This study evaluated salivary parameters, blood pressure (BP) and heart rate variability (HRV), before and after DRS treatment in edentulous patients (n=14). Collection of unstimulated and stimulated saliva, as well as blood pressure (BP) measurements and electrocardiogram recordings were performed before and after 10 days of DRS treatment. The salivary flow (mL/min) was found similar at both times while pH was smaller (more neutral) after treatment (7.3 ± 2.2 vs. 7.1 ± 0.24). Systolic BP (mmHg) showed a trend, but not a significant reduction after DRS treatment (158 ± 25.68 vs. 148 ± 16,72, p=0,062) while diastolic BP was found similar in both times (86 ± 13.93 and 84 ± 9.38). Overall HRV, measured by standard deviation of RR intervals was not affected by DRS treatment (24 ± 4 vs 18 ± 2 ms), but differences of successive RR intervals (an index of parasympathetic cardiac modulation) increased after the treatment (26 ± 4 vs 19 ± 2 ms). Moreover, another index of vagal modulation of the heart, the power of RR interval spectra at high-frequency, was also markedly higher after DRS treatment (236 ± 63 vs 135 ± 32 ms²). Such findings strongly suggest that DRS is linked to an autonomic imbalance with sympathetic overactivity, which is markedly deleterious, increasing cardiovascular risk and the incidence of diseases such as hypertension. Acknowledgment: This study is supported by FAPESP, CNPq.

Keywords: biofilm, denture stomatitis, HRV, blood pressure

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Authors: Shital Patil, Surendra Bhosale

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Cardiac diseases are the leading causes of mortality and morbidity in the world, from recent few decades accounting for a large number of deaths have emerged as the most life-threatening disorder globally. Machine learning and Artificial intelligence have been playing key role in predicting the heart diseases. A relevant set of feature can be very helpful in predicting the disease accurately. In this study, we proposed a comparative analysis of 4 different features selection methods and evaluated their performance with both raw (Unbalanced dataset) and sampled (Balanced) dataset. The publicly available Z-Alizadeh Sani dataset have been used for this study. Four feature selection methods: Data Analysis, minimum Redundancy maximum Relevance (mRMR), Recursive Feature Elimination (RFE), Chi-squared are used in this study. These methods are tested with 8 different classification models to get the best accuracy possible. Using balanced and unbalanced dataset, the study shows promising results in terms of various performance metrics in accurately predicting heart disease. Experimental results obtained by the proposed method with the raw data obtains maximum AUC of 100%, maximum F1 score of 94%, maximum Recall of 98%, maximum Precision of 93%. While with the balanced dataset obtained results are, maximum AUC of 100%, F1-score 95%, maximum Recall of 95%, maximum Precision of 97%.

Keywords: cardio vascular diseases, machine learning, feature selection, SMOTE

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Authors: Manjunatha Bangeppagari, Lee Sang Joon

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Recently, graphene-related nanomaterials are receiving fast-increasing attention with augmented applications in various fields. Especially, graphene-related materials have been widely applied to the biomedical field in the past years. In the present study, we evaluated the adverse effects of pristine graphene (pG) in zebrafish (Danio rerio) embryos in various aspects, such as mortality rate, heart rate, hatching rate, cardiotoxicity, cardiovascular defect, cardiac looping, apoptosis, and globin expression. For various trace concentrations of pG (1, 5, 10, 15, 20, 25, 30, 35, 40, 45, and 50 μg/L), early life-stage parameters were observed at 24, 48, 72, and 96 hpf. As a result, pG induces significant developmental defects including yolk sac edema, pericardial edema, embryonic mortality, delayed hatching, heartbeat, several morphological defects, pericardial toxicity, and bradycardia. Moreover, the exposure to pG was found to be a potential risk factor to the cardiovascular system of zebrafish embryos. However, further study on their properties which vary according to production methods and surface functionalization is essentially required. In addition, the possible risks of pG flakes to aquatic animals, and public health should be evaluated before releasing them to the surrounding environment.

Keywords: apoptosis, cardiovascular toxicity, globin expression, pristine graphene, zebrafish embryos

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Authors: Neeraj Malhotra

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Background: Bioreactors in tissue engineering are used as devices that apply mechanical means to influence biological processes. They are commonly employed for stem cell culturing, growth and expansion as well as in 3D tissue culture. Contemporarily there use is well established and is tested extensively in the medical sciences, for tissue-regeneration and tissue engineering of organs like bone, cartilage, blood vessels, skin grafts, cardiac muscle etc. Methodology: Literature search, both electronic and hand search, was done using the following MeSH and keywords: bioreactors, bioreactors and dentistry, bioreactors & dental tissue engineering, bioreactors and regenerative dentistry. Articles published only in English language were included for review. Results: Bioreactors like, spinner flask-, rotating wall-, flow perfusion-, and micro-bioreactors and in-vivo bioreactor have been employed and tested for the regeneration of dental and like-tissues. These include gingival tissue, periodontal ligament, alveolar bone, mucosa, cementum and blood vessels. Based on their working dynamics they can be customized in future for regeneration of pulp tissue and whole tooth regeneration. Apart from this, they have been successfully used in testing the clinical efficacy and biological safety of dental biomaterials. Conclusion: Bioreactors have potential use in testing dental biomaterials and tissue engineering approaches aimed at regenerative dentistry.

Keywords: bioreactors, biological process, mechanical stimulation, regenerative dentistry, stem cells

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Authors: Sheimah El Bejjaji, Lara Gorsek, Chandler Quilchez, Joaquim Suñer, Mireia Mallandrich

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Flurbiprofen is an anti-inflammatory drug used in several treatments. The purpose of this study was to compare the permeation of two different formulations of flurbiprofen through the human skin. The first formulation was a solution of flurbiprofen dissolved with polyethylene glycol 3350 (PEG 3350). The second formulation was flurbiprofen encapsulated in poly-ɛ-caprolactone (PɛCL) nanoparticles (NPs), stabilized with poloxamer 188, submitted individually for freeze-drying with PEG 3350 as a cryoprotectant and sterilized by gamma-irradiation. Human skin was obtained from the abdominal region of a healthy patient. The experimental protocol was approved by the Bioethics Committee of Barcelona SCIAS Hospital (Spain), and they obtained the written informed consent forms. After being frozen to -20ºC, the skin samples were cut with a dermatome at 400 µm. The ex vivo permeation study was performed in Franz diffusion cells with a diffusion area of 2.54 cm². Skin samples were placed between two compartment sites, the dermal side in contact with the receptor medium and the epidermis side in contact with the donor chamber to which the formulation was applied. The permeation study was conducted for 24 hours at 32 ± 0.5 °C in accordance with sink conditions. The results were analyzed with an unpaired t-test, and the p-values indicate the formulation with nanoparticles had a higher permeability coefficient, flux, partition parameter, diffusion parameter, and lag time. The applicability of this formulation topically can benefit articulations and ligament inflammation as an alternative to oral drugs.

Keywords: anti-inflammatory drug, flurbiprofen, human skin, nanoparticles, skin permeation

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Authors: K. P. v. R. de Silva, R. W. Senevirathna, M. M. A. J. Kumara, J. P. M. Kumarasinghe, R. L. Gunawardana, S. M. Uluwitiya, G. C. P. Jayawickrama, W. K. T. I. Madushani

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Introduction: The limited literature supporting the utilization of mechanical bowel preparation (MBP) for patients undergoing laparoscopic anterior resection (LAR) remains a notable issue. This study was conducted to examine the clinical consequences of anastomosis in colorectal surgery with MBP compared to cases where MBP was not utilized (no-MBP) in the context of LAR. Methods: This was a retrospective comparative study conducted in the professorial surgical wards of the teaching hospital karapitiya (THK). Colorectal cancer patients(n=306) participated in the study, including 151 MBP patients and 155 no-MBP patients, where the postoperative complications and mortality rates were compared. Results: The anastomotic leakage rate was 2.6%(n=4) in the no-MBP group and 6.0%(n=9) in the MBP group (p=0.143). The postoperative paralytic ileus rate was 18.5%(n=28) and 5.8%(n=9) in the MBP group and no-MBP group, respectively, displaying a statistically significant difference (p=0.001). Wound infection, pneumonia, urinary tract infection, and cardiac complication rates also were higher in the MBP group. The overall mortality rate was 1.3%(n=3) in the no-MBP group and 2.0%(n=2) in the MBP group. Conclusions: The evidence concludes that MBP increases post-operative complications. Therefore, prophylactic MBP in LAR has not been proven to benefit patients. However, further research is necessary to understand the comparative effects of MBP versus no preparation comprehensively.

Keywords: MBP, anastomosis, LAR, paralytic ileus

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Authors: Ahmed Jibrin Uttu, Maimuna Waziri

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The root bark of Glossonema boveanum (Decne), a member of Apocynaceae family, is used by traditional medicine practitioner to treat urinary and respiratory tract infections, bacteremia, typhoid fever, bacillary dysentery, diarrhea and stomach pain. This present study aims to validate the medicinal claims ascribed to the root bark of the plant. Preliminary phytochemical study of the root bark extracts (n-hexane, ethyl acetate, chloroform and methanol extracts) showed the presence of alkaloids, carbohydrates, steroids, triterpenes, cardiac glycosides, saponins, tannins and flavonoids. Antimicrobial study of the extracts showed activities against Staphylococus aureus, Bacillus subtilis, Salmonella typhii, Shigella dysenteriae, Escherichia coli, Enterobacter cloacae, Streptococcus agalactiae and Candida albicans while Micrococcus luteus, Pseudomonas aeruginosa and Klebsiella Pneumoniae showed resistance to all the extracts. The inhibitory effect was compared with the standard drug ciprofloxacin and fluconazole. MIC and MBC for both extracts were also determined using the tube dilution method. This study concluded that the root bark of G. boveanum, used traditionally as a medicinal plant, has antimicrobial activities against some causative organisms.

Keywords: Glossonema boveanum (Decne.), phytochemical, antimicrobial, minimum inhibitory concentration, minimum bactericidal concentration

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Authors: Don Buddika Oshadi Malaweera, Lora Harris, Bruce Rathgeber, Chibuike C. Udenigwe, Kirsti Rouvinen-Watt

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Fatty liver disease is among the three most severe health concerns for mink and believed to occur through the same mechanism as nursing sickness. In North America, nursing sickness affects about 45% of mink farms and in Canada, approximately 50,000 mink females is affected annually. Orotic acid (OA) plays a critical role in lipid metabolism and can increase hepatic lipids by enhancing Sterol regulatory element binding protein-1c expression and decreasing Carnitine palmitoyl transferase I activity. This study was conducted to identify particular pathways and regulatory control points involved in fatty liver development, and evaluate the effectiveness of arginine and bioactive peptides for prevention and treatment of fatty liver disease in mink. A total of 45 mink were used in 9 treatments. The experimental diets consisted of 1% OA, 2% L-arginine and 5% of whey protein hydrolysates. At the end of 10 days of experimental period, the mink were anaesthetized, sampled for blood and euthanized, samples were obtained for histological, biochemical and molecular assays. The blood samples will be analyzed for clinical chemistry and triacylglycerol. The liver samples will be analyzed for total lipid content and analyzed for 6 genes of interest involved in adipogenic transformation, ER stress, and liver inflammation.

Keywords: fatty liver, L-arginine, mink, orotic acid, whey protein hydrolysates

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Authors: Harshada Vaidya-Kannur, Dattatraya Naik

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Propolis, one of the beehive products also referred as bee-glue is sticky dark coloured complex mixture of compounds. The volatile oil can be isolated from the propolis by hydrodistillation. The mark that is left behind after the removal of volatile oil is referred as the de-oiled propolis. Antioxidant as well as anti-inflammatory properties of total ethanolic extract of de-oiled propolis (TEEDP) was investigated. Another lot of deoiled propolis was successively exacted with hexane, ethyl acetate and ethanol. Activities of these fractions were also determined. Antioxidant activity was determined by studying ABTS, DPPH and NO radical scavenging. Determination of anti-inflammatory activity was carried out by topical TPA induced mouse ear oedema model. It is noteworthy that ethyl acetate fraction of deoiled propolis (EAFDP) exhibited 49.45 % TEAC activity at the concentration 0.2 mg/ml which is equivalent to the activity of trolox at the concentration 0.2 mg/ml. Its DPPH scavenging activity (72.56%) was closely comparable to that of trolox (75%). However its NO scavenging activity was comparatively low. From IC50 values it could be concluded that the efficiency of scavenging ABTS radicals by the de-oiled propolis was more pronounced as compared to scavenging of other radicals. Studies by TPA induced mouse ear inflammation model indicated that the de-oiled propolis of Indian origin had significant topical anti-inflammatory activity. The EAFDP was found to be the most active fraction for this activity also. The purification of EAFP yielded six pure crystalline compounds. These compounds were identified by their physical data and spectral data.

Keywords: anti-inflammatory activity, anti-oxidant activity, column chromatography, de-oiled propolis

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Authors: Dylan Treger, Lujia Zhang, Xiaoxiao Jia, Jessica H. Hui, Munkh-Amgalan Gantumur, Mizhou Hui, Li Liu

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Hyaluronic acid (HA) is involved in wound healing via inflammation, granulation, and re-epithelialization mechanisms. The poor physical properties of natural high-molecular-weight polymers limit their direct use in the medical field. In this clinical study, we investigated whether the local injection of a tissue-permeable 35 kDa HA fragment (HA35) could favor the healing process in patients with chronic wounds accompanied by neuropathic pain. The HA35 fragments were freshly manufactured by degradation of high-molecular-weight HA with bovine testis-derived hyaluronidase PH20. Twenty patients in this study had nonhealing wounds and wound-related pain for more than 3 months. Freshly produced HA35 was locally injected into healthy skin immediately surrounding chronic wounds once a day for 10 days. Wound-associated pain and the degree of wound healing were evaluated. The injection of HA35 relieved the pain associated with chronic wounds in 24 hours. HA35 treatment significantly promoted the healing of chronic wounds, including expanded fresh granulation tissue on the wounds; reduced darkness or redness, dryness, and damaged areas on the surface of the skin surrounding the wounds; and decreased the size of the wound area. It can be concluded that the topical injection of tissue-permeable HA35 around chronic wounds has great potential to promote wound healing.

Keywords: 35 kDa hyaluronan fragment HA35, chronic wound, wound healing, tissue permeability

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Authors: Ali Kassem, Esam Nada, Amro Abdelhamed, Shigeo Horie

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Objective: Diabetes mellitus (DM) is associated with macrovascular complications, including coronary artery disease (CAD), and microvascular complications that contribute to the pathogenesis of erectile dysfunction (ED). On the other hand, silent myocardial ischemia (SMI) is more common in diabetic patients and is a strong predictor of cardiac events and mortality in diabetic and non-diabetic patients. Recently, Multidetector computed tomographic coronary angiography (MDCT-CA) has become a reliable non-invasive imaging modality for screening diabetic patients for SMI. We aim to evaluate the presence of SMI using (MDCT-CA) in patients with type 2DM having ED. Methods: This study evaluated 20 patients (mean age 61.45 ± 10.7 years), with DM and ED without any history of angina or angina equivalent. ED was tested with the Sexual Health Inventory for Men score, erection hardness score (EHS), and maximal penile circumferential change by an erect meter. Results: Of twenty studied patients, coronary artery stenosis was detected in 13 (65%) patients in the form of one-vessel disease (n = 6, 30%), two-vessel disease (n = 2, 10%), and three-vessel disease (n = 5, 25%). Maximum coronary artery stenosis was positively correlated with age (P < 0.016,) and negatively correlated with EHS (P <04). Multivariate regression analysis using age and EHS showed that age was the only independent predictor of SMI (P <04). Conclusion: MDCT-CA is a useful tool to identify SMI in patients with diabetes mellitus and ED. One should consider the possibility of SMI especially in elderly patients with DM who have ED.

Keywords: diabetes mellitus, erectile dysfunction, microvascular, silent ischemia

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Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan

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Background: Endothelial Progenitor Cells (EPCs) are depleted and contribute to increased cardiovascular (CV) risk in rheumatoid arthritis (RA). Statins exert a protective effect in CAD partly by promoting EPC mobilization. This vasculoprotective effect of statin has not yet been investigated in RA. We aimed to investigate the effect of rosuvastatin on EPCs in RA. Methods: 50 RA patients were randomized to receive 6 months of treatment with rosuvastatin (10 mg/day, n=25) and placebo (n=25) as an adjunct to existing stable antirheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Inflammatory measures included DAS28, CRP and ESR were measured at baseline and after treatment. Lipids and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1) were estimated at baseline and after treatment. Results: At baseline, inflammatory measures and pro-inflammatory cytokines were elevated and EPCs depleted among both groups. At baseline, EPCs inversely correlated with DAS28 and TNF-α in both groups. EPCs increased significantly (p < 0.01) after treatment with rosuvastatin but did not show significant change with placebo. Rosuvastatin exerted positive effect on lipid spectrum: lowering total cholesterol, LDL, non HDL and elevation of HDL as compared with placebo. At 6 months, DAS28, ESR, CRP, TNF-α and IL-6 improved significantly in rosuvastatin group. Significant negative correlation was observed between EPCs and DAS28, CRP, TNF-α, and IL-6 after treatment with rosuvastatin. Conclusion: First study to show that rosuvastatin improves inflammation and EPC biology in RA possibly through its anti-inflammatory and lipid lowering effect. This beneficial effect of rosuvastatin may provide a novel strategy to prevent cardiovascular events in RA.

Keywords: RA, Endothelial Progenitor Cells, rosuvastatin, cytokines

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Authors: Recep Keşli, Onur Türkyılmaz, Hayriye Tokay, Kasım Demir

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Objective: Coeliac disease (CD) is a primary small intestine disorder caused by high sensitivity to gluten which is present in the crops, characterized by inflammation in the small intestine mucosa. The goal of this study was to determine and to compare the sensitivity and specificity values of anti-endomysial IgA (EMA IgA) (IFA) and anti-tissue transglutaminase IgA (anti-tTG IgA) (ELISA) antibodies in the diagnosis of patients suspected with the CD. Methods: One thousand two hundred seventy three patients, who have applied to gastroenterology and pediatric disease polyclinics of Afyon Kocatepe University ANS Research and Practice Hospital were included into the study between 23.09.2010 and 30.05.2016. Sera samples were investigated by immunofluorescence method for EMA positiveness (Euroimmun, Luebeck, Germany). In order to determine quantitative value of Anti-tTG IgA (EIA) (Orgentec Mainz, Germany) fully automated ELISA device (Alisei, Seac, Firenze, Italy) were used. Results: Out of 1273 patients, 160 were diagnosed with coeliac disease according to ESPGHAN 2012 diagnosis criteria. Out of 160 CD patients, 120 were female, 40 were male. The EMA specificity and sensitivity were calculated as 98% and 80% respectively. Specificity and sensitivity of Anti-tTG IgA were determined as 99% and 96% respectively. Conclusion: The specificity of EMA for CD was excellent because all EMA-positive patients (n = 144) were diagnosed with CD. The presence of human anti-tTG IgA was found as a reliable marker for diagnosis and follow-up the CD. Diagnosis of CD should be established on both the clinical and serologic profiles together.

Keywords: anti-endomysial antibody, anti-tTG IgA, coeliac disease, immunofluorescence assay (IFA)

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Authors: Priyanka Sharma, Niti Puri

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Anemia develops when blood lacks enough healthy erythrocytes. Past studies indicated that anemia, inflammatory process, and oxidative stress are interconnected. Erythrocytes are continuously exposed to reactive oxygen species (ROS) during circulation, due to normal aerobic cellular metabolism and also pathology of inflammatory diseases. Systemic mastocytosis and genetic depletion of mast cells have been shown to affect anaemia. In the present study, we attempted to reveal whether mast cells have a direct role in clearance or erythrophagocytosis of normal or oxidatively damaged erythrocytes. Murine erythrocytes were treated with tert-butyl hydroperoxidase (t-BHP), an agent that induces oxidative damage and mimics in vivo oxidative stress. Normal and oxidatively damaged erythrocytes were labeled with carboxyfluorescein succinimidyl ester (CFSE) to track erythrophagocytosis. We show, for the first time, direct erythrophagocytosis of oxidatively damaged erythrocytes in vitro by RBL-2H3 mast cells as well as in vivo by murine peritoneal mast cells. Also, activated mast cells, as may be present in inflammatory conditions, showed a significant increase in the uptake of oxidatively damaged erythrocytes than resting mast cells. This suggests the involvement of mast cells in erythrocyte clearance during oxidative stress or inflammatory disorders. Partial inhibition of phagocytosis by various inhibitors indicated that this process may be controlled by several pathways. Hence, our study provides important evidence for involvement of mast cells in severe anemia due to inflammation and oxidative stress and might be helpful to circumvent the adverse anemic disorders.

Keywords: mast cells, anemia, erythrophagocytosis, oxidatively damaged erythrocytes

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Authors: Orish E. Orisakwe, Chinna N. Orish, Anthonet N. Ezejiofor

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African mesquite has been recognized for its antimicrobial, anti-inflammatory, and potential anticarcinogenic activities. However, its neuroprotective benefits against heavy metal-induced neurotoxicity remain largely unexplored. Therefore, the objective of this study was to investigate the neuroprotective properties of African mesquite in the hippocampus and olfactory bulb against common environmental pollutants, including Cd, As, Hg, and Pb. Thirty-five albino Sprague Dawley rats were divided into five groups for the experiment. Group 1 served as the control and did not receive either the heavy metal mixture (HMM) or African mesquite. Group 2 was orally administered HMM, consisting of PbCl2 (20 mg/kg), CdCl2 (1.61 mg/kg), HgCl2 (0.40 mg/kg), and NaAsO3 (10 mg/kg), for 960 days. Meanwhile, groups 3, 4, and 5 were treated with HMM along with African mesquite at doses of 500 mg/kg, 1000 mg/kg, and 1500 mg/kg, respectively. African mesquite reduced heavy metal accumulation in the hippocampus and olfactory bulb. Additionally, Sprague Dawley rats exhibited improved performance in the Passive avoidance and Cincinnati Maze tests. Furthermore, treatment with African mesquite significantly alleviated inflammation macromolecules peroxidation. It also restored the concentrations of SOD, CAT, GSH, GPx, Hmox-1, and reduced the activity of AChE, NRF2 and NFkB and improved histopathological findings. African mesquite exhibits a multifaceted neuroprotective effect with the potential to mitigate various aspects of heavy metal-induced neurotoxicity.

Keywords: African mesquite, heavy metal mixture;, neurotoxicity;, chemoprevention

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Authors: Ahmad Shah Farhat

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Background: Prenatal asphyxia or birth asphyxia is the medical situation resulting from a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. Human umbilical cord blood (UCB) is a well-established source of hematopoietic stem/progenitor cells (HSPCs) for allogeneic stem cell transplantation. These can be used clinically to care for children with malignant diseases. Low O2 can cause in proliferation and differentiation of stem cells. Method: the cord blood of 11 infants with 3-5 Apgar scores or need to cardiac pulmonary Resuscitation as an asphyxia group and ten normal infants with more than 8 Apgar scores as the normal group was collected, and after isolating hematopoietic stem cells, the cells were cultured in enriched media for 14 days to compare the numbers of colonies by microscope. Results: There was a significant difference in the number of RBC precursor colonies (red colonies) in cultured media with 107 cord blood hematopoietic stem cells of infants who were exposed to hypoxemia in two wells of palate. There was not a significant difference in the number of white cell colonies in the two groups in the two wells of the plate. Conclusion: Hypoxia in the perinatal period can cause the increase of hematopoietic stem cells of cord blood, special red precursor stem cells in vitro, like an increase of red blood cells in the body when exposed to low oxygen conditions. Thus, it will be usable.

Keywords: asphyxia, neonre, stem cell, red cell

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Authors: Raluca Popescu, Diana Costinel, Elisabeta-Irina Geana, Oana-Romina Botoran, Roxana-Elena Ionete, Yazan Falah Jadee 'Alabedallat, Mihai Botu

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Walnut production is high in Romania, different varieties being cultivated dependent on high yield, disease resistance or quality of produce. Walnuts have a highly nutritional composition, the kernels containing essential fatty acids, where the unsaturated fraction is higher than in other types of nuts, quinones, tannins, minerals. Walnut consumption can lower the cholesterol, improve the arterial function and reduce inflammation. The purpose of this study is to determine and compare the composition of walnuts of indigenous and international varieties all grown in Romania, in order to identify high-quality indigenous varieties. Oil has been extracted from the nuts of 34 varieties, the fatty acids composition and IV (iodine value) being afterwards measured by NMR. Furthermore, δ13C of the extracted oil had been measured by IRMS to find specific isotopic fingerprints that can be used in authenticating the varieties. Chemometrics had been applied to the data in order to identify similarities and differences between the varieties. The total saturated fatty acids content (SFA) varied between n.d. and 23% molar, oleic acid between 17 and 35%, linoleic acid between 38 and 59%, linolenic acid between 8 and 14%, corresponding to iodine values (IV - total amount of unsaturation) ranging from 100 to 135. The varieties separated in four groups according to the fatty acids composition, each group containing an international variety, making possible the classification of the indigenous ones. At both ends of the unsaturation spectrum, international varieties had been found.

Keywords: δ13C-IRMS, fatty acids composition, 1H-NMR, walnut varieties

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Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

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The 18-kDa translocator protein (TSPO) previously called as peripheral benzodiazepine receptor, is proven biomarker for variety of neuroinflammation. TSPO is tryptophane rich five transmembranal protein found on outer mitochondrial membrane of steroid synthesising and immunomodulatory cells. In case of neuronal damage or inflammation the expression level of TSPO get upregulated as an immunomodulatory response. By utilizing Benzoxazolone as a basic scaffold, series of TSPO ligands have been designed followed by their screening through in silico studies. Synthesis has been planned by employing convergent methodology in six high yielding steps. For the synthesized ligands the ‘in vitro’ assay was performed to determine the binding affinity in term of Ki. On ischemic rat brain, autoradiography studies were also carried to check the specificity and affinity of the designed radiolabelled ligand for TSPO.Screening was performed on the basis of GScore of CADD based schrodinger software. All the modified and better prospective compound were successfully carried out and characterized by spectroscopic techniques (FTIR, NMR and HRMS). In vitro binding assay showed best binding affinity Ki = 6.1+ 0.3 for TSPO over central benzodiazepine receptor (CBR) Ki > 200. ARG studies indicated higher uptake of two analogues on the lesion side compared with that on the non-lesion side of ischemic rat brains. Displacement experiments with unlabelled ligand had minimized the difference in uptake between the two sides which indicates the specificity of the ligand towards TSPO receptor.

Keywords: TSPO, PET, imaging, Acetamidobenzoxazolone

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Authors: Ewa Rusak, Sebastian Seget, Aleksandra Mroskowiak, Mirosław Partyka, Ewa Samulska, Julia Strózik, Anna Wilk, Przemysława Jarosz-Chobot

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Introduction: Various infections can affect children suffering from Type 1 Diabetes (T1D) because of dysfunctions of the immune system. The urinary tract and urethra of these children can be easily infected areas because of glycosuria. Aim: The microflora assessment of the urethra area of children with newly diagnosed T1D. Methods: The materials of the study were swabs taken prospectively from the urethral area of 63 children at the time of diagnosis of T1D (37 boys), then the results were correlated to the clinical parameters. In the statistical analysis, there were T student, Chi square, and U Mann-Whitney tests used. Results: The mean age was 9.4 years (6 months-17.4 years). The mean HbA1c value was 12.1% (5,6% - 20.1%). The mean value of glycosuria was 4463.2 mg/dl (0 - 9770 mg/dl). Ketoacidosis was diagnosed in 29 children (49%). The following microbial species were isolated in the collected materials: Staphylococcus epidermidis in 18 children (28.6%), Enterococcus faecalis in 17 children (27%), Candida albicans in 15 children (23.8%), coagulase-negative staphylococciin 11 children (17.5%), group B Streptococcus beta-hemolysis in 10 children (15.9%), S. aureus, E. coli, S. anginosus, C. glucuronolyticum, and A. urinae in 7 children each (11.1%), group B Streptococcus beta-hemolysis and S. hominis in 6 children each (9.5%), L. gasseri in 5 children (7.5%), C. dubliniensis in 4 children (6.3) and other, isolated cases. 2 of diagnosed patients were cultured negatively (3.2%). There were statistical correlations between the type of colonisation and patients’ sex and HbA1C value. Conclusions: It is extremely important to examine the urethral area at the time of diagnosis of T1D in order to detect inflammation and to undertake the appropriate and effective intervention.

Keywords: diabetology, skin disorders, microbiology, microflora

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Authors: Gehan F. Abdel Raoof, Ataa A. Said, Khaled Y. Mohamed, Hala M. Mohammed

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Pleiogynium timorense(DC.) Leenh is one of the therapeutically active plants belonging to the family Anacardiaceae. The bark of Pleiogynium timorense needs further studies to investigate its phytochemical and biological activities. This work was carried out to investigate the chemical composition of petroleum ether extract of Pleiogynium timorense bark as well as to evaluate the analgesic and anti-inflammatory activities. The unsaponifiable matter and fatty acid methyl esters were analyzed by Gas chromatography–mass spectrometry (GC-MS). Moreover, analgesic and anti-inflammatory activities were evaluated using acetic acid-induced writhing test and carrageen hind paw oedema models in rats, respectively. The results showed that twenty one compounds in the unsaponifiable fraction were identified representing 92.54 % of the total beak area, the major compounds were 1-Heptene (35.32%), Butylated hydroxy toluene (19.42%) and phytol (12.53%), whereas fifteen compounds were identified in the fatty acid methyl esters fraction representing 94.15% of the total identified peak area. The major compounds were 9-Octadecenoic acid methyl ester (35.34%) and 9,12-Octadecadienoic acid methyl ester (29.32%). Moreover, petroleum ether extract showed a significant reduction in pain and inflammation in a dose dependent manner. This study aims to be the first step toward the use of petroleum ether extract of Pleiogynium timorense bark as analgesic and anti-inflammatory drug.

Keywords: analgesic, anti-inflammatory, bark, petroleum ether extract, Pleiogynium timorense

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Authors: I. Boroňová, J. Bernasovská, J. Kmec, E. Petrejčíková

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Dilated cardiomyopathy (DCM) is a severe cardiovascular disorder characterized by progressive systolic dysfunction due to cardiac chamber dilatation and inefficient myocardial contractility often leading to chronic heart failure. Recently, a genome-wide association studies (GWASs) on DCM indicate that the ZBTB17 gene rs10927875 single nucleotide polymorphism is associated with DCM. The aim of the study was to identify the distribution of ZBTB17 gene rs10927875 polymorphism in 50 Slovak patients with DCM and 80 healthy control subjects using the Custom Taqman®SNP Genotyping assays. Risk factors detected at baseline in each group included age, sex, body mass index, smoking status, diabetes and blood pressure. The mean age of patients with DCM was 52.9±6.3 years; the mean age of individuals in control group was 50.3±8.9 years. The distribution of investigated genotypes of rs10927875 polymorphism within ZBTB17 gene in the cohort of Slovak patients with DCM was as follows: CC (38.8%), CT (55.1%), TT (6.1%), in controls: CC (43.8%), CT (51.2%), TT (5.0%). The risk allele T was more common among the patients with dilated cardiomyopathy than in normal controls (33.7% versus 30.6%). The differences in genotype or allele frequencies of ZBTB17 gene rs10927875 polymorphism were not statistically significant (p=0.6908; p=0.6098). The results of this study suggest that ZBTB17 gene rs10927875 polymorphism may be a risk factor for susceptibility to DCM in Slovak patients with DCM. Studies of numerous files and additional functional investigations are needed to fully understand the roles of genetic associations.

Keywords: ZBTB17 gene, rs10927875 polymorphism, dilated cardiomyopathy, cardiovascular disorder

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Authors: Kathryn Norgang, Sarah Howrath, Auni Idi Muhire, Pacifique Umubyeyi

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Description : A group of nurses address the shortage of trained staff to respond to critical patients at Rwanda Military Hospital (RMH) by developing a training program and a resuscitation response team. Members of the group who received the training when it first launched are now trainer of trainers; all components of the training program are organized and delivered by RMH staff-the clinical mentor only provides adjunct support. This two day training is held quarterly at RMH; basic life support and exposure to interventions for advanced care are included in the test and skills sign off. Seventy staff members have received the training this year alone. An increased number of admission/transfer to ICU due to successful resuscitation attempts is noted. Lessons learned: -Number of staff trained 2012-2014 (to be verified). -Staff who train together practice with greater collaboration during actual resuscitation events. -Staff more likely to initiate BLS if peer support is present-more staff trained equals more support. -More access to Advanced Cardiac Life Support training is necessary now that the cadre of BLS trained staff is growing. Conclusions: Increased access to training, peer support, and collaborative practice are effective strategies to strengthening resuscitation capacity within a hospital.

Keywords: resuscitation, basic life support, capacity building, resuscitation response teams, nurse trainer of trainers

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Authors: Surarong Chinwong, Namthip Intarakumhang Na Rachasima, Siyaporn Kuikhiew, Dujrudee Chinwong

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Irrational use of medicines is a major problem in public health. Half of all patients take medicines incorrectly. An inappropriate use of antibiotics is one of the common types of irrational medicine use; for example, patients use antibiotic for treatment of common cold or diarrhea. Objectives: This cross-sectional study aimed to investigate the behaviors on antibiotic use, using amoxicillin and norfloxacin as examples, as well as sources of received health information. Methods: An online self-administered questionnaire was used to collect data from participants in Thailand between September and December 2015. Participants were asked about their behaviors on antibiotic use. Data were analyzed using descriptive statistics. Results: Of all 405 participants, most were female (65.3 %), aged 18-30 years (49.4 %), undergraduate or lower (69.7%), and civil servant or state enterprises (31.7 %). We found inappropriate behaviors in use of amoxicillin or norfloxacin: 1) there were 201/400 participants (50.3%) taking amoxicillin right away in case of having a common cold, such as having sore throat, running nose, and cough; 2) there were 170/405 participants (42.0%) using amoxicillin for relieving inflammatory symptoms, e.g. muscle inflammation or osteoarthritis; 3) there were 71/398 participants (17.8%) using amoxicillin as a muscle relaxant; 4) there were 135/398 participants (33.9%) using norfloxacin for treating diarrhea. Sources of health information received by the participants were from the internet (78.5%), the radio and/or television (42.2%), advertising publishing (33.3 %), and word of mouth (30.1%). Conclusion: This study showed improper behaviors in antibiotic use especially amoxicillin and norfloxacin. Health care providers including pharmacists should raise the public awareness on dangers of inappropriate antibiotic use and promote the rational use of antibiotics.

Keywords: antibiotic use, amoxicillin, norfloxacin, rational drug use

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Authors: Ghada E. Esheba, Ghadeer F. Alharthi, Duaa A. Alhejaili, Rawan E. Hudairy, Wafaa A. Altaezi, Raghad M. Alhejaili

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Background: Inflammatory bowel disease (IBD) consists of two specific gastrointestinal disorders: ulcerative colitis (UC) and Crohn's disease (CD). Despite their distinct natures, these two diseases share many similar etiologic, clinical and pathological features, as a result, their accurate differential diagnosis may sometimes be difficult. Correct diagnosis is important because surgical treatment and long-term prognosis differ from UC and CD. Aim: This study aims to study the characteristic clinicopathological features which help in the differential diagnosis between UC and CD, and assess the disease activity in ulcerative colitis. Materials and methods: This study was carried out on 50 selected cases. The cases included 27 cases of UC and 23 cases of CD. All the cases were examined using H& E and immunohistochemically for bcl-2 expression. Results: Characteristic features of UC include: decrease in mucous content, irregular or villous surface, crypt distortion, and cryptitis, whereas the main cardinal histopathological features seen in CD were: epitheloid granuloma, transmural chronic inflammation, absence of mucin depletion, irregular surface, or crypt distortion. 3 cases of UC were found to be associated with dysplasia. UC mucosa contains fewer Bcl-2+ cells compared with CD mucosa. Conclusion: This study using multiple parameters such clinicopathological features and Bcl-2 expression as studied by immunohistochemical stain, helped to gain an accurate differentiation between UC and CD. Furthermore, this work spotted the light on the activity and different grades of UC which could be important for the prediction of relapse.

Keywords: Crohn's disease, dysplasia, inflammatory bowel disease, ulcerative colitis

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Authors: Rahul Madathiparambil Visalakshan, Alex Cavallaro, John Hayball, Krasimir Vasilev

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The role of biomaterial surface nanotopograhy on fibrinogen adsorption and unfolding, and the subsequent immune response were studied. Inconsistent topography and varying chemical functionalities along with a lack of reproducibility pose a challenge in determining the specific effects of nanotopography or chemistry on proteins and cells. It is important to have a well-defined nanotopography with a homogeneous chemistry to study the real effect of nanotopography on biological systems. Therefore, we developed a technique that can produce well-defined and highly reproducible topography to identify the role of specific roughness, size, height and density with the presence of homogeneous chemical functionality. Using plasma polymerisation of oxazoline monomers and immobilized gold nanoparticles we created surfaces with an equal number density of nanoparticles of different sizes. This surface was used to study the role of surface nanotopography and the interplay of surface chemistry on proteins and immune cells. The effect of nanotopography on fibrinogen adsorption was investigated using Quartz Cristal Microbalance with Dissipation and micro BCA. The mass of fibrinogen adsorbed on the surface increased with increasing size of nano-topography. Protein structural changes up on adsorption to the nano rough surface was studied using circular dichroism spectroscopy. Fibrinogen unfolding varied depending on the specific nanotopography of the surfaces. It was revealed that the in vitro immune response to the nanotopography surfaces changed due to this protein unfolding.

Keywords: biomaterial inflammation, protein and cell responses, protein unfolding, surface nanotopography

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Authors: Kriyapa lairungruang, Arunporn Itharat

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Limonia acidissima L. (LA) (Common name: wood apple, Thai name: ma-khwit) is a medicinal plant which has long been used in Thai traditional medicine. Its bark is used for treatment of diarrhea, abscess, wound healing and inflammation and it is also used in oral cancer. Thus, this research aimed to investigate antioxidant and cytotoxic activities of the LA bark extracts produced by various extraction methods. Different extraction procedures were used to extract LA bark for biological activity testing: boiling in water, maceration with 95% ethanol, maceration with 50% ethanol and water boiling of each the 95% and the 50% ethanolic residues. All extracts were tested for antioxidant activity using DPPH radical scavenging assay, cytotoxic activity against human laryngeal epidermoid carcinoma (HEp-2) cells and human oral epidermoid carcinoma (KB) cells using sulforhodamine B (SRB) assay. The results found that the 95% ethanolic extract of LA bark showed the highest antioxidant activity with EC50 values of 29.76±1.88 µg/ml. For cytotoxic activity, the 50% ethanolic extract showed the best cytotoxic activity against HEp-2 and KB cells with IC50 values of 9.55±1.68 and 18.90±0.86 µg/ml, respectively. This study demonstrated that the 95% ethanolic extract of LA bark showed moderate antioxidant activity and the 50% ethanolic extract provided potent cytotoxic activity against HEp-2 and KB cells. These results confirm the traditional use of LA for the treatment of oral cancer and laryngeal cancer, and also support its ongoing use.

Keywords: antioxidant activity, cytotoxic activity, Laryngeal epidermoid carcinoma, Limonia acidissima L., oral epidermoid carcinoma

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Authors: Jiandong Ren, Lijun Zhao, Peng Chen

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Nafamostat (NA), a synthetic broad-spectrum serine protease inhibitor, has been routinely employed for the treatment of acute pancreatitis (AP) and other inflammatory-associated diseases in some East Asia countries. Although the potent inhibitory activity against inflammation-related proteases such as thrombin, trypsin, kallikrein, plasmin, coagulation factors and complement factors is generally considered to be responsible for the anti-inflammatory effects of NA, precise target and molecular mechanism underlying the anti-inflammatory activity in the treatment of AP remain largely unknown yet. As an intracellular inflammatory signaling platform, the NOD-like receptor protein 3 (NLRP3) inflammasome is recently identified to be involved in the development of AP. In present study, we have revealed that NA alleviated pancreatic injury in a caerulein-induced AP model by inhibiting the NLRP3 inflammasome activation in pancreas. Mechanistically, NA interacted with HDAC6, a cytoplasmic deacetylase implicated in the NLRP3 inflammasome pathway, and efficiently abrogated the function of HDAC6. This property enabled NA to influence HDAC6 dependent NF-κB transcriptional activity and thus block NF-κB-driven transcriptional priming of NLRP3 inflammasome. Moreover, NA exerted the potential to interfere HDAC6-mediated intracellular transport of NLRP3, thereby leading to the failure of NLRP3 inflammasome activation. Our current work has provided valuable insight into the molecular mechanism underlying the immunomodulatory effect of NA in treatment of AP, highlighting its promising application in prevention of NLRP3 inflammasome-associated inflammatory pathological damage.

Keywords: acute pancreatitis, HDAC6, nafamostat, NLRP3 inflammasome

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