Search results for: liver biopsy

Authors: Ahlem Bahi, Youcef Necib, Sakina Zerizer, Cherif Abdennour, Mohamed Salah Boulakoud

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Mercury (II) is a highly toxic metal which induces oxidative stress in the body. In this study, we aimed to investigate the possible protective effect of olive oil, an antioxidant agent, against experimental mercury toxicity in rat model. Administration of mercuric chloride induced significant increase in serum: ALT, AST, and LPA activities; interleukine1, interleukine6, tumor necrosis factor α (TNFα), creatinine, urea, and uric acid levels. Mercuric chloride also induced oxidative stress, as indicate by decreased tissue of GSH level, GSH-Px, and GST activities along with increase the level of lipid peroxidation. Furthermore, treatment with mercuric chloride caused a marked elevation of kidney and liver weight and decreased body weight. Virgin olive oil treatment markedly reduced elevated serum: AST, ALT, and LPA activities; interleukine1, interleukine6, tumor necrosis factor α (TNFα), creatinine, urea, and uric acid levels and contracted the deterious effects of mercuric chloride on oxidative stress markers changes caused by HgCl2 in tissue as compared to control group. Our results implicate that mercury induced oxidative damage in liver and kidney tissue protected by virgin olive oil, with its antioxidant effects.

Keywords: mercury, antioxidant enzymes, pro-inflammatory cytokine, virgin olive oil, lipid peroxidation

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Authors: Wassim Guermazi, Saoussan Boukhris, Neila Annabi Trabelsi, Tarek Rebai, Alya Sellami-Kamoun, Habib Ayadi

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This work investigates the protective effects of the microalga Halamphora sp. extract (H. Ext) as a natural product on lead-intoxicated liver and kidney human cells in vitro and in vivo on rats wistar. HepG2 cells line derived from human hepatocellular carcinoma and HEK293 cells line derived from human embryonic kidney were used for the in vitro study. The analysis of the fatty acids methyl esters of the extract was performed by a GC/MS. Four groups of rats, each of which was composed of six animals, were used for the in vivo experiment. The pretreatment of HepG2 and HEK293 cells line with the extract (100 µg mL-1) significantly (p < 0.05) protected against cytotoxicity induced by lead exposure. In vivo, the biochemical parameters in serum, namely malondialdehyde level (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities, were measured in supernatants of organ homogenates. H. Ext was found to be rich in fatty acids, essentially palmitic and palmitoleic accounting respectively 29.46% and 42.07% of total fatty acids. Both in vitro and in vivo, the co-treatment with H. Ext allowed the protection of the liver and kidney cells structure, as well as the significant preservation of normal antioxidant and biochemical parameters in rats. Halamphora extract rich in fatty acids has been proven to be effective in protection against Pb-induced toxicity.

Keywords: microalga extract, human cells line, fatty acid, lead exposure, oxidative stress, rats

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Authors: So Young Kim, Eun-Young Kwon, Bora Choi, Mi Kyeong Yu, Seon Jeong Lee, Myung-Sook Choi

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Lemon (Citrus limon) has various beneficial effect. Eriocitrin (eriodictyol 7-rutinoside) is the main ingredient of lemon fruit and is known to have antioxidative effects. However, there has been little research about the effects of eriocitrin on obesity and regulation of lipid profiles levels. In the present study, we investigated the anti-obesity and lipid-lowering effects of eriocitrin in mice fed high-fat diet (HFD). The 4 week-old male C57BL/6 mice were randomly divided into two groups and were fed HFD (20% fat, w/w) and HFD supplemented with eriocitrin (0.005%, w/w, EC) for 16 weeks. Food intake, body weight and white adipose tissue weight (WAT) were measured and plasma free fatty acid (FFA), apolipoprotein (Apo) B100 level and hepatic enzyme activity were analyzed. No differences were shown between the HFD and EC groups in body weight and food intake. However EC supplementation significantly reduced the weights of epididymal, subcutaneous and total WAT. In addition, the levels of plasma FFA and Apo B100 were significantly decreased in the EC group compared with the HFD group. Moreover, the activities of glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) related to fatty acids synthesis were significantly lower in the EC group than in the HFD group in liver. Therefore, this study indicates that eriocitrin has beneficial effects on adiposity and nonalcholic fatty liver diseases by modulating hepatic lipid-regulating enzyme activities and plasma lipid profile.

Keywords: antiobesity, eriocitrin, high fat diet, lipid lowering

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Authors: Naomi Sakamoto, Eisuke Fukuma, Mika Nashimoto, Yoshitomo Koshida

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Background: Selective localization of the metastatic lymph node with clip and removal of clipped nodes with sentinel lymph node (SLN), known as targeted axillary dissection (TAD), reduced false-negative rates (FNR) of SLN biopsy (SLNB) after neoadjuvant chemotherapy (NAC). For the patients who achieved nodal pathologic complete response (pCR), accurate staging of axilla by TAD lead to omit axillary lymph node dissection (ALND), decreasing postoperative arm morbidity without a negative effect on overall survival. This study aimed to investigate the ultrasound (US) identification rate and success removal rate of two kinds of ultrasound-visible clips placed in metastatic lymph nodes during TAD procedure. Methods: This prospective study was conducted using patients with clinically T1-3, N1, 2, M0 breast cancer undergoing NAC followed by surgery. A US-visible clip was placed in the suspicious lymph node under US guidance before neoadjuvant chemotherapy. Before surgery, US examination was performed to evaluate the detection rate of clipped node. During the surgery, the clipped node was removed using several localization techniques, including hook-wire localization, dye-injection, or fluorescence technique, followed by a dual-technique SLNB and resection of palpable nodes if present. For the fluorescence technique, after injection of 0.1-0.2 mL of indocyanine green dye (ICG) into the clipped node, ICG fluorescent imaging was performed using the Photodynamic Eye infrared camera (Hamamatsu Photonics k. k., Shizuoka, Japan). For the dye injection method, 0.1-0.2 mL of pyoktanin blue dye was injected into the clipped node. Results: A total of 29 patients were enrolled. Hydromark™ breast biopsy site markers (Hydromark, T3 shape; Devicor Medical Japan, Tokyo, Japan) was used in 15patients, whereas a UltraCor™ Twirl™ breast marker (Twirl; C.R. Bard, Inc, NJ, USA) was placed in 14 patients. US identified the clipped node marked with the UltraCore Twirl in 100% (14/14) and with the Hydromark in 93.3% (14/15, p = ns). Success removal of clipped node marked with the UltraCore Twirl was achieved in 100% (14/14), whereas the node marked with the Hydromark was removed in 80% (12/15) (p = ns). Conclusions: The ultrasound identification rate differed between the two types of ultrasound-visible clips, which also affected the success removal rate of clipped nodes. Labelling the positive node with a US-highly-visible clip allowed successful TAD.

Keywords: breast cancer, neoadjuvant chemotherapy, targeted axillary dissection, breast tissue marker, clip

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Authors: Hala Demerdash, Ola M. Zanaty, Emad Eldin Arida

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Background: This study investigated the micoRNA expression changes induced by Sevoflurane and Propofol and their effects on liver functions. Patients and methods: The study was designed as randomized controlled study, carried out on 200 adult patients, scheduled for major surgeries under general anesthesia (GA). Patients were randomly divided into four groups; groups SC and PC included chronic hepatitis C (CHC) patients where SC group are patients receiving Sevoflurane, and PC group are patients receiving Propofol anesthesia. While S and P groups included non- hepatitis patients; S group are patients receiving Sevoflurane and P group are patients receiving Propofol. Anesthesia in Group S and SC patients was maintained by sevoflurane, while anesthesia in Group P and PC patients was maintained by propofol infusion. Blood samples were analyzed for PT, PTT and liver enzymes. Serum samples were analyzed for microRNA before and after surgery. Results: Results show miRNA-122 and miRNA-21 were absent in serum of S and P groups in pre-operative samples. However, they were expressed in SC and PC groups. In post-operative samples; miRNA-122 revealed an increased expression in all groups; with more exaggerated response in SC group. On the other hand miRNA-21 revealed increased expression in both SC and PC groups; a slight expression in S group with absent expression in P group. There was a post-operative negative correlation between miR-122 and ALT (r=-0.46) in SC group and (r=-0.411) in PC group and positive correlation between ALT and miR-21 (r=0.335) in SC group and (r=0.379) in PC group. The amount of blood loss was positively correlated with miR-122 (r=0.366) in SC group and (r=0.384) in PC group. Conclusion: Propofol anesthesia is safer than Sevoflurane anesthesia in patients with CHC. Sevoflurane and Propofol anesthesia affect miRNA expression in both CHC and non-hepatitis patients.

Keywords: anesthesia, chronic hepatitis C, micoRNA, propofol, sevoflurane

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Authors: Pornrut Rabintossaporn, Suphaket Saenthaweesuk, Amornnat Thuppia, Nuntiya Somparn

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Several dietary and herbal plants have been shown to possess cytoprotective and antioxidant effects with various mechanisms of action. The aim of this study was to determine the antioxidant effects and its mechanism of aqueous leaves extract of Ocimum americanum (OA), commonly known as American basil or 'hoary basil', in rat. The extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with the extract at the dose of 100, 200 and 400 mg/kg for 28 days. Phytochemical screening of plant extracts revealed the presence of alkaloid, cardiac glycosides, tannin and steroid compounds. The extract contained phenolic compounds 36.91 ± 0.66 mg of gallic acid equivalents per gram OA extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 41.27 ± 1.86 µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14µg/mL. In the animals, the extract was well tolerated by the animals throughout the 28 days of study as shown by normal serum levels AST, ALP, ALT, BUN and Cr as well as normal histology of liver and pancreatic and kidney tissue. The protein expression of antioxidant enzymes, γ-glutamylcysteine ligase (γ-GCL) in liver was significantly increased compared with normal control. Consistent with the induction of γ-GCL protein expression significantly reduction of serum oxidative stress marker malondialdehyde (MDA) was found in rat treated with OA extract compared with control. Taken together, this study provides evidence that Ocimum americanum exhibits direct antioxidant properties and can induce cytoprotective enzyme in vivo.

Keywords: antioxidant, γ-glutamylcysteine ligase, MDA, Ocimum americanum

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Authors: Fahimeh Palizban, Farshad Noravesh, Amir Hossein Saeidian, Mahya Mehrmohamadi

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In the recent decade, the emergence of liquid biopsy has significantly improved cancer monitoring and detection. Dying cells, including those originating from tumors, shed their DNA into the blood and contribute to a pool of circulating fragments called cell-free DNA. Accordingly, identifying the tissue origin of these DNA fragments from the plasma can result in more accurate and fast disease diagnosis and precise treatment protocols. Open chromatin regions are important epigenetic features of DNA that reflect cell types of origin. Profiling these features by DNase-seq, ATAC-seq, and histone ChIP-seq provides insights into tissue-specific and disease-specific regulatory mechanisms. There have been several studies in the area of cancer liquid biopsy that integrate distinct genomic and epigenomic features for early cancer detection along with tissue of origin detection. However, multimodal analysis requires several types of experiments to cover the genomic and epigenomic aspects of a single sample, which will lead to a huge amount of cost and time. To overcome these limitations, the idea of predicting OCRs from WGS is of particular importance. In this regard, we proposed a computational approach to target the prediction of open chromatin regions as an important epigenetic feature from cell-free DNA whole genome sequence data. To fulfill this objective, local sequencing depth will be fed to our proposed algorithm and the prediction of the most probable open chromatin regions from whole genome sequencing data can be carried out. Our method integrates the signal processing method with sequencing depth data and includes count normalization, Discrete Fourie Transform conversion, graph construction, graph cut optimization by linear programming, and clustering. To validate the proposed method, we compared the output of the clustering (open chromatin region+, open chromatin region-) with previously validated open chromatin regions related to human blood samples of the ATAC-DB database. The percentage of overlap between predicted open chromatin regions and the experimentally validated regions obtained by ATAC-seq in ATAC-DB is greater than 67%, which indicates meaningful prediction. As it is evident, OCRs are mostly located in the transcription start sites (TSS) of the genes. In this regard, we compared the concordance between the predicted OCRs and the human genes TSS regions obtained from refTSS and it showed proper accordance around 52.04% and ~78% with all and the housekeeping genes, respectively. Accurately detecting open chromatin regions from plasma cell-free DNA-seq data is a very challenging computational problem due to the existence of several confounding factors, such as technical and biological variations. Although this approach is in its infancy, there has already been an attempt to apply it, which leads to a tool named OCRDetector with some restrictions like the need for highly depth cfDNA WGS data, prior information about OCRs distribution, and considering multiple features. However, we implemented a graph signal clustering based on a single depth feature in an unsupervised learning manner that resulted in faster performance and decent accuracy. Overall, we tried to investigate the epigenomic pattern of a cell-free DNA sample from a new computational perspective that can be used along with other tools to investigate genetic and epigenetic aspects of a single whole genome sequencing data for efficient liquid biopsy-related analysis.

Keywords: open chromatin regions, cancer, cell-free DNA, epigenomics, graph signal processing, correlation clustering

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Authors: S. Jaramillo, Y. Montoya, W. Agudelo, J. Bustamante

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Cardiovascular diseases (CVD) are related to affectations of the heart and blood vessels, within these are pathologies such as coronary or peripheral heart disease, caused by the narrowing of the vessel wall (atherosclerosis), which is related to the accumulation of Low-Density Lipoproteins (LDL) in the arterial walls that leads to a progressive reduction of the lumen of the vessel and alterations in blood perfusion. Currently, the main therapeutic strategy for this type of alteration is drug treatment with statins, which inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), responsible for modulating the rate of cholesterol production and other isoprenoids in the mevalonate pathway. This enzyme induces the expression of LDL receptors in the liver, increasing their number on the surface of liver cells, reducing the plasma concentration of cholesterol. On the other hand, when the blood vessel presents stenosis, a surgical procedure with vascular implants is indicated, which are used to restore circulation in the arterial or venous bed. Among the materials used for the development of vascular implants are Dacron® and Teflon®, which perform the function of re-waterproofing the circulatory circuit, but due to their low biocompatibility, they do not have the ability to promote remodeling and tissue regeneration processes. Based on this, the present research proposes the development of a hydrolyzed collagen and polyethylene oxide electrospun membrane reinforced with medium and high-intensity statins, so that in future research it can favor tissue remodeling processes from its microarchitecture.

Keywords: atherosclerosis, medium and high-intensity statins, microarchitecture, electrospun membrane

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Authors: Beom-Seok Ko, Yoo-Seok Kim, Woo-Sung Lim, Ku-Sang Kim, Hyun-Ah Kim, Jin-Sun Lee, An-Bok Lee, Jin-Gu Bong, Tae-Hyun Kim, Sei-Hyun Ahn

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Background: Breast conserving surgery (BCS) followed by radiation therapy is today standard therapy for early breast cancer. It is safe therapeutic procedure in early breast cancers, because it provides the same level of overall survival as mastectomy. There are a number of different types of incisions used to BCS. Avoiding scars on the breast is women’s desire. Numerous minimal approaches have evolved due to this concern. Periareolar incision is often used when the small tumor relatively close to the nipple. But periareolar incision has a disadvantages include limited exposure of the surgical field. In plastic surgery, various methods such as zigzag incisions have been recommended to achieve satisfactory esthetic results. Periareolar zigzag incision has the advantage of not only good surgical field but also contributed to better surgical scars. The purpose of this study was to evaluate the oncological safety of procedures by studying the status of the surgical margins of the excised tumor specimen and reduces the need for further surgery. Methods: Between January 2016 and September 2016, 148 women with breast cancer underwent BCS or mastectomy by the same surgeon in ASAN medical center. Patients with exclusion criteria were excluded from this study if they had a bilateral breast cancer or underwent resection of the other tumors or taken axillary dissection or performed other incision methods. Periareolar zigzag incision was performed and excision margins of the specimen were identified frozen sections and paraffin-embedded or permanent sections in all patients in this study. We retrospectively analyzed tumor characteristics, the operative time, size of specimen, the distance from the tumor to nipple. Results: A total of 148 patients were reviewed, 72 included in the final analysis, 76 excluded. The mean age of the patients was 52.6 (range 25-19 years), median tumor size was 1.6 cm (range, 0.2-8.8), median tumor distance from the nipple was 4.0 cm (range, 1.0-9.0), median excised specimen sized was 5.1 cm (range, 2.8-15.0), median operation time was 70.0 minute (range, 39-138). All patients were discharged with no sign of infection or skin necrosis. Free resection margin was confirmed by frozen biopsy and permanent biopsy in all samples. There were no patients underwent reoperation. Conclusions: We suggest that periareolar zigzag incision can provide a good surgical field to remove a relatively large tumor and may provide cosmetically good outcomes.

Keywords: periareolar zigzag incision, breast conserving surgery, breast cancer, resection margin

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Authors: Ahmet Uyar, Zabit Yener, Abdulahad Dogan

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(1). The ameliorative potential and antioxidant capacity of an extract of Urtica dioica seeds (UDS) were investigated using histopathological changes in liver and kidney of broiler, measuring serum marker enzymes, antioxidant defence systems and lipid peroxidation (malondialdehyde (MDA)) content in various tissues of broilers exposed to aflatoxin (AF). (2). A total of 32 broilers were divided randomly into 4 groups: control, UDS extract-treated, AF-treated and AF+UDS extract-treated. Broilers in control and UDS extract-treated groups were fed on a diet without AF. The AF-treated group and AF+UDS extract-treated groups were treated with an estimated 1 mg total AF/kg feed. The AF+UDS extract groups received in addition 30 ml UDS extract/kg diet for 21 days. (3). The AF-treated group had significantly decreased body weight gain when compared to the other groups. (4). Biochemical analysis showed a small increase in the concentrations of serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase and lactate dehydrogenase in the AF-treated group compared to that of the control group, whereas concentrations of these enzymes were decreased in the AF+UDS group compared to that of the AF-treated group. (5). Administration of supplementary UDS extract helped restore the AF-induced increase in MDA and reduced the antioxidant system towards normality, particularly in the liver, brain, kidney and heart. Hepatorenal protection by UDS extracts was further supported by the almost normal histology in AF +UDS extract-treated group as compared to the degenerative changes in the AF-treated broilers. (6). It was concluded that UDS extract has a protective hepatorenal effect in broilers affected by aflatoxicosis, probably acting by promoting the antioxidative defence systems.

Keywords: aflatoxicosis, biochemistry, broiler, histopathology, Urtica dioica seed extract

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Jin Choi, Zahra Aminikhoei, Yi-Oh Kim, Sang-Min Lee

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A 4 × 2 factorial experiment was conducted to determine the optimum dietary protein and lipid levels for juvenile fancy carp, Cyprinus carpio var. koi. Eight experimental diets were formulated to contain four protein levels (200, 300, 400, and 500 g kg-1) with two lipid levels (70 and 140 g kg-1). Triplicate groups of fish (initial weight, 12.1±0.2 g fish-1) were hand-fed the diets to apparent satiation for 8 weeks. Weight gain, daily feed intake, feed efficiency ratio and protein efficiency ratio were significantly (P < 0.0001) affected by dietary protein level, but not by dietary lipid level (P > 0.05). Weight gain and feed efficiency ratio tended to increase as dietary protein level increased up to 400 and 500 g kg-1, respectively. Daily feed intake of fish decreased with increasing dietary protein level and that of fish fed diet contained 500 g kg-1 protein was significantly lower than other fish groups. The protein efficiency ratio of fish fed 400 and 500 g kg-1 protein was lower than that of fish fed 200 and 300 g kg-1 protein. Moisture, crude protein and crude lipid contents of muscle and liver were significantly affected by dietary protein, but not by dietary lipid level (P > 0.05). The increase in dietary lipid level resulted in an increase in linoleic acid in liver and muscle paralleled with a decrease in n-3 highly unsaturated fatty acids content in muscle of fish. In considering these results, it was concluded that the diet containing 400 g kg-1 protein with 70 g kg-1 lipid level is optimal for growth and efficient feed utilization of juvenile fancy carp.

Keywords: fancy carp, dietary protein, dietary lipid, Cyprinus carpio, fatty acid

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Authors: Rotimi Larayetana, Yahaya Abdulrazaq, Oladunni O. Falola, Abayomi Ajayi

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The aim of this study was to perform green synthesis of silver nanoparticles (AgNPs) with the aqueous extract of Moringa oleifera Lam (M oleifera) leaves and determine its effects on benign prostatic hyperplasia in Wistar rats. Silver nitrate (AgNO₃) solution was reduced using the aqueous extract of Moringa oleifera Lam leaves, the resultant biogenic AgNPs were characterized by Fourier transformed infrared spectrophotometric, SEM, TEM and X-ray diffraction analysis. Animal experiments involved thirty (30) adult male Wistar rats randomly divided into five groups (A to E; n ₌ 5). Group A received only subcutaneous injection of olive oil daily while the other groups got 3 mg/kg/daily of testosterone propionate (TP) subcutaneously plus 50 mg/kg/daily of AgNPs intraperitoneally (B), 3 mg/kg/daily of TP plus 25 mg/kg/daily of AgNPs (C), 3 mg/kg/daily of TP only (D) and 25 mg/kg/daily of AgNPs only (E). The animals were sacrificed after 14 days, and the prostate gland, liver, and kidney were processed for histological analysis. Phytochemical screening and GC-MS analysis were performed to determine the composition of the M oleifera extract used. Biogenic AgNPs with an average diameter of 23 nm were synthesized. Biogenic AgNPs ameliorated hormone-induced prostate enlargement, and the inhibition of prostatic hypertrophy could be due to the presence of a significant amount of plant fatty acids and phytosterols in the aqueous extract of M oleifera extract. However, the administration of biogenic AgNPs at higher doses impacted negatively on the cytoarchitecture of the liver. Green synthesis of AgNPs with the aqueous extract of Moringa oleifera might be beneficial for the treatment of BPH.

Keywords: benign prostatic hyperplasia, biogenic synthesis, Moringa oleifera, silver nanoparticles, testosterone

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Authors: Salma Baig, Bakrudeen Ali Ahmad, Ainnul Hamidah Syahadah Azizan, Hapipah Mohd Ali, Elham Rouhollahi, Mahmood Ameen Abdulla

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Free radical damage induced by reactive oxygen species (ROS) contributes to etiology of many chronic diseases, cancer being one of them. Recent studies have been successful in ROS targeted therapies via antioxidants using mouse models in cancer therapeutics. The present study was designed to scrutinize anticancer activity, antioxidant activity of 5 different extracts of Thymus serpyllum in MDA-MB-231, MCF-7, HepG2, HCT-116, PC3, and A549. Identification of the phytochemicals present in the most active extract of Thymus serpyllum was conducted using gas chromatography coupled with mass spectrophotometry and antioxidant activity was measured by using DPPH radical scavenging and FRAP assay. Anticancer impact of the extract in terms of IC50 was evaluated using MTT cell viability assay. Results revealed that the hexane extract showed the best anticancer activity in HepG2 (Liver Carcinoma Cell Line) with an IC50 value of 23 ± 0.14 µg/ml followed by 25 µg/ml in HCT-116 (Colon Cancer Cell Line), 30 µm/ml in MCF-7 (Breast Cancer Cell Line), 35 µg/ml in MDA-MB-231 (Breast Cancer Cell Line), 57 µg/ml in PC3 (Prostate Cancer Cell Line) and 60 µg/ml in A549 (Lung Carcinoma Cell Line). GC-MS profile of the hexane extract showed the presence of 31 compounds with carvacrol, thymol and thymoquione being the major compounds. Phenolics such as Vitamin E, terpinen-4-ol, borneol and phytol were also identified. Hence, here we present the first report on cytotoxicity of hexane extract of Thymus serpyllum extract in HepG2 cell line with a robust anticancer activity with an IC50 of 23 ± 0.14 µg/ml.

Keywords: Thymus serpyllum L., hexane extract, GC-MS profile, antioxidant activity, anticancer activity, HepG2 cell line

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Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

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New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

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Authors: Thinakar Mani Balusamy, Venkateswaran A. R., Bharat Narasimhan, Ratnakar Kini S., Kani Sheikh M., Prem Kumar K., Pugazhendi Thangavelu, Arun Murugan, Sibi Thooran Karmegam, Radhakrishnan N., Mohammed Noufal, Amit Soni

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Background and Aims: The liver is integral to lipid metabolism, and a compromise in its function leads to perturbations in these pathways. In this study, we hope to determine the correlation between CLD severity and its effect on lipid parameters. We also look at the etiology-specific effects on lipid levels. Materials and Methods: This is a retrospective cross-sectional analysis of 250 patients with cirrhosis compared to 250 healthy age and sex-matched controls. Severity assessment of CLD using MELD and Child-Pugh scores was performed and etiological details collected. A questionnaire was used to obtain patient demographic details and lastly, a fasting lipid profile (Total, LDL, HDL cholesterol, Triglycerides and VLDL) was obtained. Results: All components of the lipid profile declined linearly with increasing severity of CLD as determined by MELD and Child-Pugh scores. Lipid levels were clearly lower in CLD patients as compared to healthy controls. Interestingly, preliminary analysis indicated that CLD of different etiologies had differential effects on Lipid profiles. This aspect is under further analysis. Conclusion: All components of the lipid profile were definitely lower in CLD patients as compared to controls and demonstrated an inverse correlation with increasing severity. The utilization of this parameter as a prognosticating aid requires further study. Additionally, preliminary analysis indicates that various CLD etiologies appear to have specific effects on the lipid profile – a finding under further analysis.

Keywords: CLD, cholesterol, HDL, LDL, lipid profile, triglycerides, VLDL

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Authors: Khelladi Hadj Mostefa, Krouf Djamil, Taleb-Dida Nawel

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Background: Obesity results from a prolonged imbalance between energy intake and energy expenditure, as depending on basal metabolic rate. Oils and proteins from sea have important therapeutic (such as obesity and hypercholesterolemia) and antioxidant effects. Sardine are a widely consumed fish in the Mediterranean region. Its consumption provides humans with various nutrients such as oils (rich in omega 3 plyunsaturated fatty acids)) and proteins. Methods: Sardine oil (SO) and sardine proteins (SP) were extracted and purified. Mixture of vegetable oils (olive-walnut-sunflower) were prepared from oils produced in Algeria. Eighteen wistar rats are fed a high fat diet enriched with 1% cholesterol for 30 days to induce obesity and hypercholesterolemia. The rats are divided into 3 groups. The first group consumes 20% sardine protein combined with 5% sardine oil (38% SFA (saturated fatty acids), 31% MIFA (monounsaturated fatty acids) and 31% PIFA (polyunsaturated fatty acids)) (SPso). The second group consumes 20% sardine protein combined with 5% of a mixture of vegetable oils (VO) containing 13% SFA, 58% MIFA and 29% PIFA (PSvo), and the third group consuming 20% casein combined with 5% of the mixture of vegetable oils and serves as a semi-synthetic reference (CASvo). Body weights and glycaemia are measured weekly After 28 days of experimentation, the rats are sacrificed, the blood and the liver removed. Serum assays of total cholesterol (TC) and triglycerides (TG) were performed by enzymatic colorimetric methods. Evaluation of lipid peroxidation was performed by assaying thiobarbituric acid reactive species (TBARS) and hydroperoxides values. The protein oxidation was performed by assaying carbonyl derivatives values. Finally, evaluation of antioxidant defense is made by measuring the activity of antioxidant enzymes, the superoxide dismutase (SOD) and the catalase (CAT).Results: After 28 days, the body weight (BW) of the rats increased significantly in SPso and SPvo groups compared to CAS group, by +11% and 7%, respectively. Cholesterolemia (TC) increased significantly in the SPso and SPvo groups compared to the CAS group (P<0.01), while triglyceridemia (TG) decreased significantly in the SPso group compared to SPvo and CAS groups (P<0.01). Albumin (marker of inflammation) increased in the PSs group compared to SPvo and CAS groups by +35% and +13%, respectively. The serum TBARS levels are -40% lower in SPso group compared to SPvo group, and they are -80% and -76% lower in SPso compared to SPvo and CAS groups, respectively. The level of carbonyls derivatives in the serum and liver are significantly reduced in the SPso group compared to the SPvo and CAS groups. Superoxide dismutase (SOD) activity decreased in liver of SPso group compared to SPvo group (P<0.01). While that of CAT is increased in liver tissue of SPso group compared to SPvo group (P<0.01). Conclusion: Sardine oil combined with sardine protein has a hypotriglyceridemic effect, reduces body weight, attenuates inflammation and seems to protect against lipid peroxidation and protein oxidation and increases antioxidant defense in hypercholesterolemic and obese rats. This could be in favor of a protective effect against obesity and cardiovascular diseases.

Keywords: rat, obesity, hypercholesterolemia, sardine protein, sardine oil, vegetable oils mixture, lipid peroxidation, protein oxidation, antioxidant defense

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Authors: Ji Su Kim, Bo Ram Choi, Ju Yeon Cho, Hyukjin Lee

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Epidermal growth factor receptor (EGFR) 19 deletion mutation gene is over-expressed in carcinoma patient. EGFR 19 deletion mutation is known as typical biomarker of non-small cell lung cancer (NSCLC), which one section in the coding exon 19 of EGFR is deleted. Therefore, there have been many attempts over the years to detect EGFR 19 deletion mutation for replacing conventional diagnostic method such as PCR and tissue biopsy. We developed a simple and facile detection platform based on Rolling Circle Amplification (RCA), which provides highly amplified products in isothermal amplification of the ligated DNA template. Limit of detection (~50 nM) and a faster detection time (~30 min) could be achieved by introducing RCA.

Keywords: EGFR19, cancer, diagnosis, rolling circle amplification (RCA), hydrogel

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Authors: Bassant M. M. Ibrahim, Doha H. Abou Baker, Ahmed Abd Elghafour

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Excessive exposure to heavy metals contributes to the occurrence of deleterious health problems that affect vital organs like the brain, liver, kidneys, and heart. The use of natural products that have antioxidant capabilities may contribute to the protection of these organs. In the present study, the essential oil of summer savory (Satureja hortensis) was used to evaluate its protective effects against lead acetate induced damaging effect on rats’ vital organs, due to its high contents of carvacrol, y-terpinene, and p-cymene. Forty female Wister Albino rats were classified into five equal groups, the 1st served as normal group, the 2nd served as positive control group was given lead acetate (60 mg/kg) intra-peritoneal (IP), the third to fifth groups were treated with calcium disodium (EDTA) as chelating agent and summer savory essential oil in doses of (50 and 100mg/kg) respectively. All treatments were given IP concomitant with lead acetate for ten successive days. At the end of the experiment duration electrocardiogram (ECG), an open field test for the evaluation of psychological state, rotarod test as for the evaluation of locomotor coordination ability as well as anti-inflammatory and oxidative stress biomarkers in serum and histopathology of vital organs were performed. The investigations in this study show that the protective effect of high dose of summer savory essential oil is more than the low dose and that the essential oil of summer savory is a promising agent that can contribute to the protection of vital organs against the hazardous damaging effects of lead acetate.

Keywords: brain, heart, kidneys, lead acetate, liver, protective, summer savory

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Authors: Nirali Sanghavi, Julia Ash, Amy Wasserman

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Introduction: To the best of our knowledge, there is only one case report that found an association between leuprolide and scleroderma renal crisis (SRC). Leuprolide has been noted to cause acute renal failure in some patients. Given the close timing of the leuprolide injection and the worsening renal function in our patient, leuprolide likely caused exacerbation of lupus nephritis and SRC. Interestingly, our patient on long-term hydroxychloroquine (HCQ) with normal baseline cardiac function was found to have HCQ cardiomyopathy highlighting the need for close monitoring of HCQ toxicity. We know that some of the risk factors that are involved in HCQ induced cardiomyopathy are older age, females, increased dose and >10 years of HCQ use, and pre-existing cardiac and renal insufficiency. Case presentation: A 34-year-old African American woman with a history of overlap of systemic lupus erythematosus (SLE) and scleroderma features and class III lupus nephritis presented with severe headaches, elevated blood pressure (180/120 mmHg) and worsening creatinine levels (2.07 mg/dL). The headaches started 1 month ago after she started leuprolide injections for fibroids. She was being treated with mycophenolate mofetil 1 gm twice a day, belimumab weekly, HCQ 200mg, and prednisone 5 mg daily. She has been on HCQ since her teenage years. The examination was unremarkable except for proximal interphalangeal joint contractures in the right hand and sclerodactyly of bilateral hands, unchanged from baseline. Laboratory findings include urinalysis, which showed 3+ protein, 1+ blood, 6 red blood cells, and 14 white blood cells ruling out thrombotic microangiopathy. C3 was 32 mg/dL, C4 <5 mg/dL, and +dsDNA increased >1000. She was started on captopril and discharged once creatinine and blood pressure was controlled. She was readmitted with hypertension, hyperkalemia, worsening creatinine, nephrotic range proteinuria, complaints of chest pressure, and shortness of breath with pleuritic chest pain. Physical examination and lab findings were unchanged. She was treated with pulse dose methyl prednisone followed by taper and multiple anti-hypertensive agents, including captopril, for presumed lupus nephritis flare versus SRC. Renal biopsy was consistent with SRC and class IV lupus nephritis and was started on cyclophosphamide. While cardiac biopsy showed borderline myocarditis without necrosis and cytoplasmic vacuolization consistent with HCQ cardiomyopathy, hence HCQ was discontinued. Summary: It highlights a rare association of leuprolide causing exacerbation of lupus nephritis or SRC. Although rare, the current case reinforces the importance of close monitoring for HCQ toxicity in patients with renal insufficiency.

Keywords: leuprolide, lupus nephritis, scleroderma, SLE

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Authors: Xu Yifei, Le Yining, Yang Qingluan, Tu Yanjie

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Objective: This study aims to investigate the distribution features of Traditional Chinese Medicine (TCM) syndromes and syndrome elements in Epstein-Barr virus-associated diseases and then explores the relations between TCM syndromes or syndrome elements and laboratory indicators of Epstein-Barr virus-associated diseases. Methods: A cross-sectional study of 70 patients with EBV infection was described. We assessed the diagnostic information and laboratory indicators of these patients from Huashan Hospital Affiliated to Fudan University between November 2017 and July 2019. The disease diagnosis and syndrome differentiation were based on the diagnostic criteria of EBV-associated diseases and the theory of TCM respectively. Confidence correlation analysis, logistic regression analysis, cluster analysis, and the Sankey diagram were used to analyze the correlation between the data. Results: The differentiation of the 4 primary TCM syndromes in the collected patients was correlated with the indexes of immune function, liver function, inflammation, and anemia, especially the relationship between Qifen syndrome and high lactic acid dehydrogenase level. The common 11 TCM syndrome elements were associated with the increased CD3+ T cell rate, low hemoglobin level, high procalcitonin level, high lactic acid dehydrogenase level, and low albumin level. Conclusion: The changes in immune function indexes, procalcitonin, and liver function-related indexes in patients with EBV-associated diseases were consistent with the evolution law of TCM syndromes. This study provides a reference for judging the pathological stages of these kinds of diseases, predicting their prognosis, and guiding subsequent treatment strategies based on TCM syndrome type.

Keywords: EBV-associated diseases, traditional Chinese medicine syndrome, syndrome element, diagnostics

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Authors: Mosaab A. Omara, Layla O. Elmajdoubb, Mohammad Saleh Al-Aboodyc, Ahmed ElSifyd, Ahmed O. Elkhtamd

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The aim of this study is to present the molecular characterization of cysticercus tenuicolis of Taenia hydatigena from livestock isolates in Egypt, using the amplification of sequencing of the mt-CO1 gene. We introduce a detailed image of the Cysticercus tenuicolis infection in ruminant animals in Upper Egypt. Cysticercus tenuicolis inhabits such organs in ruminants as the omentum, viscera, and liver. In the present study, the infection rate of Cysticercus tenuicolis was found to be 16% and 19% in sheep and goat sample respectively. Firstly we report one larval stage of Taenia hydatigena detected in the camel liver in Egypt. Cysticercus tenuicolis infection manifested a higher prevalence in females than in males. Those above 2 years of age manifested a higher infection rate than younger animals. The preferred site for the infection was the omentum: a 70% preference in sheep and a 68% preference in goat samples. The molecular characterization using the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene of isolates from sheep, goats and camels corresponded to T. hydatigena. For this study, molecular characterizations of T. hydatigena were done for the first time in Egypt. Molecular tools are of great assistance in characterizing the Cysticercus tenuicolis parasite especially when the morphological character cannot be detected because the metacestodes are frequently confused with infection by the Hydatid cyst, especially when these occur in the visceral organs. In the present study, Cysticercus tenuicolis manifested high identity in the goat and sheep samples, while differences were found more frequently in the camel samples (10 pairbase). Clearly molecular diagnosis for Cysticercus tenuicolis infection significantly helps to differentiate it from such other metacestodes.

Keywords: cysticercus tenuicolis, its2, genetic, qena, molecular and taenia hydatigena

Procedia PDF Downloads 523

Authors: Eyup Ozkan, Ozkan U. Nalbantoglu, Aycan Gundogdu, Mehmet Hora, A. Emre Onuk

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The human microbiome has been associated with cardiological conditions and this relationship is becoming to be defined beyond the gastrointestinal track. In this study, we investigate the alteration in circulatory microbiota in the context of Coronary Artery Disease (CAD). We received circulatory blood samples from suspected CAD patients and maintain 16S ribosomal RNA sequencing to identify each patient’s microbiome. It was found that Corynebacterium and Methanobacteria genera show statistically significant differences between healthy and CAD patients. The overall biodiversities between the groups were observed to be different revealed by machine learning classification models. We also achieve and demonstrate the performance of a diagnostic method using circulatory blood microbiome-based estimation.

Keywords: coronary artery disease, blood microbiome, machine learning, angiography, next-generation sequencing

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Authors: Girum Tedla Assefa

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Background: Granulomatous mycosis fungoides is an extremely rare type of cutaneous T-cell lymphoma (<55 cases reported worldwide). Case report: A 36-year-old female presented with soft tissue atrophy of right lower limb (dermis + hypodermis) of 22 years and plaques over trunk of 3 years duration. Histological examination of a biopsy taken from the atrophied tissue showed a granulomatous reaction with epidermotropic atypical lymphocytes. However, in other areas there were only findings of conventional MF without granuloma. Conclusion: The diagnosis of a granulomatous mycosis fungoides depends exclusively on the histological demonstration of granulomas. Distinct clinical characteristics are not present. This case highlights the importance of thorough investigation of lipoatrophic skin changes in the adult to exclude underlying causes, including MF.

Keywords: cutaneous lymphoma, granulomatous skin lymphoma, mycoses fungoides, skin atrophy

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Authors: Sulyman Abdulhakeem Olarewaju, S. O. Malomo, M. T. Yakubu, J. O. Akolade

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The ameliorative effect of Celosia argentea var. cristata leaf extract against cadmium (Cd) induced oxidative stress and toxicity in selected tissues of rats was investigated. Toxicity coupled with oxidative stress was induced in rats by oral administration of Cd (8 mg/kg b. wt). Preliminary quantitative phytochemical and in vitro antioxidant analyses showed that the methanolic extract of C. argentea leaves was constituted by polyphenols (5.72%), saponins (3.20%), tannins (0.65%) and cadenolides (0.006%). IC50 of 9800, 7406, and 45.04 μg/ml were recorded for inhibition of linoleic acid oxidation, 2, 2-diphenyl-1-picrylhydrazyl and hydrogen peroxide radicals respectively. Simultaneous administration of C. argentea leaf extract with Cd significantly attenuated Cd-induced elevation of serum enzyme markers such as aspartate and alanine transaminase, alkaline and acid phosphatase as well as γ-glutaryltransferase in a dose-dependent fashion, while their reduced level in the liver were significantly increased. Higher levels of enzymatic antioxidants; superoxide dismutase and catalase activities were observed in the liver, brain, kidney and testes of the Cd-induced rats treated with C. argentea extract, while lipid peroxidation expressed in malondialdehyde concentrations were lower when compared to values in rats administered Cd only. Other Cd-induced toxicity and stress markers in the serum viz. reduced uric acid and albumin levels as well as elevated total and unconjugated bilirubin were attenuated by the extract and their values compared favorably with those animals co-administered cadmium with ascorbic acid. Data from the study showed that oral administration of extract from the leaf C. argentea may ameliorate Cd-induced oxidative stress and toxicity in rats.

Keywords: toxicity, cadmium, celosia, antioxidants, oxidative stress

Procedia PDF Downloads 346

Authors: Ati Moncef

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We describe in this paper the results of a phantom of dynamics renal with MAG3. Our phantom consisted of (tow shaped of kidneys, 1 liver). These phantoms were scanned with static and dynamic protocols and compared with clinical data. in a normal conditions we use our phantoms it's possible to acquire a renal images when we can be compared with clinical scintigraphy. In conclusion, Renal phantom also can use in the quality control of a renal scintigraphy.

Keywords: Renal scintigraphy, MAG3, Nuclear medicine, Gamma Camera.

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Authors: Nurlaili E. P., Astuti M., Marsono Y., Naruki S.

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Iron is an essential nutrient with limited bioavailability. Nutritional anemia caused mainly by iron deficiency is the most recognized nutritional problem in both countries as well as affluent societies. Rice (Oryza sativa L.) has become the most important cereal crop for the improvement of human health due to the starch, protein, oil, and the majority of micronutrients, particularly in Asian countries. In this study, the iron availability and profile lipid were evaluated for the extracts from Cibeusi varieties (black rices) of ancient rice brans. Results: The quality of K, B, R, E diets groups shows the same effect on the growth of rats. This indicate that groups is as efficiently utilized by the body as E diets. Hematocrit and MCHC levels of rats fed K, B, R and E diets were not significantly (P< 0.05). MCV and MCH levels of rats K, B, R were significantly (P< 0.05) with E groups but rats K, B, R were not significantly (P< 0.05). The iron content in the serum of rats fed with K, B, R and E diets were not significantly (P< 0.05). The highest level of iron in the serum was founded in the B group. The iron content in the liver of rats fed with K, B, R and E diets were not significantly (P< 0.05). The highest level of iron in the liver was founded in the R group. HDL cholesterol levels were significantly (P< 0.05) between rats of fed B, E with K, R, but K and R were not significantly (P< 0.05). LDL cholesterol levels of rats fed K and E significantly (P< 0.05) with B and R. Conclusions: the bran of pigmented rice varieties has, with some exceptions, greater antioxidant and free-radical scavenging activities. The results also show that pigmented rice extracts acted as pro-oxidants in the lipid peroxidation assay, possibly by mechanisms described for the pro-oxidant activities of tocopherol and ascorbic. Pigmented rice bran extracts more effectively increases iron stores and reduces the prevalence of iron deficiency. And reduces cholesterol, TG and LDL cholesterol and increses HDL cholesterol.

Keywords: anemia, black rice bran extract, iron, profile lipid

Procedia PDF Downloads 484

Authors: M. S. Hasni, J. Guan, K. Yakimchuk, M. Berglund, B. Sander, G. Enblad, R. M. Amini, S. Okret

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Lymphomas are generally not considered as endocrine-related cancers. However, most lymphoid malignancies show gender differences in incidence and show prognosis with males being more affected. Furthermore, some epidemiological data indicate a protective role of estrogens against Non-Hodgkin lymphomas. Recent studies have demonstrated estrogen receptor β (ERβ) to be the major ER expressed in normal and malignant cells of lymphoid origin. We have analyzed the effects of estradiol and selective ERα and ERβ agonists on lymphoma growth in culture and in vivo. Treating lymphoma cells with estradiol or ERα selective agonist had minor or no effect on cell growth while selective ERβ agonist treatment showed an antiproliferative effect. When grafting mice with murine T lymphoma cells, male mice developed larger tumors compared to female mice, a difference that was abolished following ovariectomy, demonstrating estrogen-dependent growth in vivo. When subcutaneously grafting lymphoma cells to mice, so far growth of all tested human B lymphoma tumors (Raji and Ramos Burkitt lymphoma, SU.DHL4 (GC) and U2932 (ABC) DLBCL, Granta-519, Maver1 and Z138 MCL cells), were reduced following treatment with ERβ selective agonist (ref. 2 and unpublished). Moreover, the number and size of liver foci of disseminating Raji cells was reduced. We have identified target genes and mechanism that could explain the above effects of ERβ agonists. This included effects on angio and lymphangiogenesis. Now we have further analyzed effects of ERβ agonists on Ibrutinib-sensitive and -insensitive MCL cells in xenograft experiments as well as ERβ expression in primary lymphoma material (DLBCL). Preliminary statistical analysis has been done correlating ERβ expression to other biomarkers and clinical data.

Keywords: lymphomas, estrogen receptors, cancer, liver foci

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Authors: Lena Lapidot, Amir Amnon, Rita Nosenko, Veitsman Ella, Cohen-Ezra Oranit, Davidov Yana, Segev Shlomo, Koren Omry, Safran Michal, Ben-Ari Ziv

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Introduction: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related mortality worldwide. Liver Cirrhosis is the main predisposing risk factor for the development of HCC. The factor(s) influencing disease progression from Cirrhosis to HCC remain unknown. Gut microbiota has recently emerged as a major player in different liver diseases, however its association with HCC is still a mystery. Moreover, there might be an important association between the gut microbiota, nutrition, life style and the progression of Cirrhosis and HCC. The aim of our study was to characterize the gut microbial signature in association with life style and nutrition of patients with Cirrhosis, HCC-Cirrhosis and healthy controls. Design: Stool samples were collected from 95 individuals (30 patients with HCC, 38 patients with Cirrhosis and 27 age, gender and BMI-matched healthy volunteers). All participants answered lifestyle and Food Frequency Questionnaires. 16S rRNA sequencing of fecal DNA was performed (MiSeq Illumina). Results: There was a significant decrease in alpha diversity in patients with Cirrhosis (qvalue=0.033) and in patients with HCC-Cirrhosis (qvalue=0.032) compared to healthy controls. The microbiota of patients with HCC-cirrhosis compared to patients with Cirrhosis, was characterized by a significant overrepresentation of Clostridium (pvalue=0.024) and CF231 (pvalue=0.010) and lower expression of Alphaproteobacteria (pvalue=0.039) and Verrucomicrobia (pvalue=0.036) in several taxonomic levels: Verrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae and the genus Akkermansia (pvalue=0.039). Furthermore, we performed an analysis of predicted metabolic pathways (Kegg level 2) that resulted in a significant decrease in the diversity of metabolic pathways in patients with HCC-Cirrhosis (qvalue=0.015) compared to controls, one of which was amino acid metabolism. Furthermore, investigating the life style and nutrition habits of patients with HCC-Cirrhosis, we found significant correlations between intake of artificial sweeteners and Verrucomicrobia (qvalue=0.12), High sugar intake and Synergistetes (qvalue=0.021) and High BMI and the pathogen Campylobacter (qvalue=0.066). Furthermore, overweight in patients with HCC-Cirrhosis modified bacterial diversity (qvalue=0.023) and composition (qvalue=0.033). Conclusions: To the best of the our knowledge, we present the first report of the gut microbial composition in patients with HCC-Cirrhosis, compared with Cirrhotic patients and healthy controls. We have demonstrated in our study that there are significant differences in the gut microbiome of patients with HCC-cirrhosis compared to Cirrhotic patients and healthy controls. Our findings are even more pronounced because the significantly increased bacteria Clostridium and CF231 in HCC-Cirrhosis weren't influenced by diet and lifestyle, implying this change is due to the development of HCC. Further studies are needed to confirm these findings and assess causality.

Keywords: Cirrhosis, Hepatocellular carcinoma, life style, liver disease, microbiome, nutrition

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Authors: Rojith K. Balakrishnan

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Plasmablastic lymphoma (PBL) is an uncommon, recently described B-cell derived lymphoma that is most commonly seen in patients with Human Immunodeficiency Virus (HIV) infection. Here we report a case of PBL in a 35 year old man with HIV who presented with multiple subcutaneous swellings all over the body and oral mucosal lesions.The biopsy report was suggestive of Diffuse Large B Cell Lymphoma. Immunohistochemistry was done which showed, lymphoma cells, positive for MUM1, CD 138, and VS 38. The proliferation index (MIB) was 95%. Final report was consistent with the diagnosis of Plasmablastic Lymphoma. The lesion completely regressed after treatment with systemic chemotherapy. Up to date, only a few cases of plasmablastic lymphoma have been reported from India. Increased frequency of this lymphoma in HIV patients and rarity of the tumour, along with rapid response of the same to chemotherapy, make this case a unique one. Hence the knowledge about this new entity is important for clinicians who deal with HIV patients.

Keywords: human immunodeficiency virus (HIV), oral cavity lesion, plasmablastic lymphoma, subcutaneous swelling

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