Search results for: oral epidermoid carcinoma

Authors: Isabel Lopez-Oliva, Akshay Paropkari, Shweta Saraswat, Stefan Serban, Paola de Pablo, Karim Raza, Andrew Filer, Iain Chapple, Thomas Dietrich, Melissa Grant, Purnima Kumar

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Objective: We aimed to explicate the role of the subgingival microbiome in the causal link between rheumatoid arthritis (RA) and periodontitis (PD). Methods: Subjects with/without RA and with/without PD were randomized for treatment with scaling and root planing (SRP) or oral hygiene instructions. Subgingival biofilm, gingival crevicular fluid, and serum were collected at baseline and at 3- and 6-months post-operatively. Correlations were generated between 72 million 16S rDNA sequences, immuno-inflammatory mediators, circulating antibodies to oral microbial antigens, serum inflammatory molecules, and clinical metrics of RA. The dynamics of inter-microbial and host-microbial interactions were modeled using differential network analysis. Results: RA superseded periodontitis as a determinant of microbial composition, and DAS28 score superseded the severity of periodontitis as a driver of microbial assemblages (p=0.001, ANOSIM). RA subjects evidenced higher serum anti-PPAD (p=0.0013), anti-Pg-enolase (p=0.0031), anti-RPP3, anti- Pg-OMP and anti- Pi-OMP (p=0.001) antibodies than non-RA controls (with and without periodontitis). Following SRP, bacterial networks anchored by IL-1b, IL-4, IL-6, IL-10, IL-13, MIP-1b, and PDGF-b underwent ≥5-fold higher rewiring; and serum antibodies to microbial antigens decreased significantly. Conclusions: Our data suggest a circular relationship between RA and PD, beginning with an RA-influenced dysbiosis within the healthy subgingival microbiome that leads to exaggerated local inflammation in periodontitis and circulating antibodies to periodontal pathogens and positive correlation between severity of periodontitis and RA activity. Periodontal therapy restores host-microbial homeostasis, reduces local inflammation, and decreases circulating microbial antigens. Our data highlights the importance of integrating periodontal care into the management of RA patients.

Keywords: rheumatoid arthritis, periodontal, subgingival, DNA sequence analysis, oral microbiome

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Authors: Emma R. Arakelova, Stepan G. Grigoryan, Flora G. Arsenyan, Nelli S. Babayan, Ruzanna M. Grigoryan, Natalia K. Sarkisyan

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Novel nanosize zinc oxide composites of doxorubicin obtained by deposition of 180 nm thick zinc oxide film on the drug surface using DC-magnetron sputtering of a zinc target in the form of gels (PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO) were studied for drug delivery applications. The cancer specificity was revealed both in in vitro and in vivo models. The cytotoxicity of the test compounds was analyzed against human cancer (HeLa) and normal (MRC5) cell lines using MTT colorimetric cell viability assay. IC50 values were determined and compared to reveal the cancer specificity of the test samples. The mechanistic study of the most active compound was investigated using Flow cytometry analyzing of the DNA content after PI (propidium iodide) staining. Data were analyzed with Tree Star FlowJo software using cell cycle analysis Dean-Jett-Fox module. The in vivo anticancer activity estimation experiments were carried out on mice with inoculated ascitic Ehrlich’s carcinoma at intraperitoneal introduction of doxorubicin and its zinc oxide compositions. It was shown that the nanosize zinc oxide film deposition on the drug surface leads to the selective anticancer activity of composites at the cellular level with the range of selectivity index (SI) from 4 (Starch+NaCMC+Dox+ZnO) to 200 (PEO(gel)+Dox+ZnO) which is higher than that of free Dox (SI = 56). The significant increase in vivo antitumor activity (by a factor of 2-2.5) and decrease of general toxicity of zinc oxide compositions of doxorubicin in the form of the above mentioned gels compared to free doxorubicin were shown on the model of inoculated Ehrlich's ascitic carcinoma. Mechanistic studies of anticancer activity revealed the cytostatic effect based on the high level of DNA biosynthesis inhibition at considerable low concentrations of zinc oxide compositions of doxorubicin. The results of studies in vitro and in vivo behavior of PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO composites confirm the high potential of the nanosize zinc oxide composites as a vector delivery system for future application in cancer chemotherapy.

Keywords: anticancer activity, cancer specificity, doxorubicin, zinc oxide

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Authors: Omar Youssef, Aija Knuuttila, Paivi Piirilä, Virinder Sarhadi, Sakari Knuutila

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Exhaled breath condensate (EBC) is a unique sample that allows studying different genetic changes in lung carcinoma through a non-invasive way. With the aid of next generation sequencing (NGS) technology, analysis of genetic mutations has been more efficient with increased sensitivity for detection of genetic variants. In order to investigate the possibility of applying this method for cancer diagnostics, mutations in EBC DNA from lung cancer patients and healthy individuals were studied by using NGS. The key aim is to assess the feasibility of using this approach to detect clinically important mutations in EBC. EBC was collected from 20 healthy individuals and 9 lung cancer patients (four lung adenocarcinomas, four 8 squamous cell carcinoma, and one case of mesothelioma). Mutations in hotpot regions of 22 genes were studied by using Ampliseq Colon and Lung cancer panel and sequenced on Ion PGM. Results demonstrated that all nine patients showed a total of 19 cosmic mutations in APC, BRAF, EGFR, ERBB4, FBXW7, FGFR1, KRAS, MAP2K1, NRAS, PIK3CA, PTEN, RET, SMAD4, and TP53. In controls, 15 individuals showed 35 cosmic mutations in BRAF, CTNNB1, DDR2, EGFR, ERBB2, FBXW7, FGFR3, KRAS, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, and TP53. Additionally, 45 novel mutations not reported previously were also seen in patients’ samples, and 106 novel mutations were seen in controls’ specimens. KRAS exon 2 mutations G12D was identified in one control specimen with mutant allele fraction of 6.8%, while KRAS G13D mutation seen in one patient sample showed mutant allele fraction of 17%. These findings illustrate that hotspot mutations are present in DNA from EBC of both cancer patients and healthy controls. As some of the cosmic mutations were seen in controls too, no firm conclusion can be drawn on the clinical importance of cosmic mutations in patients. Mutations reported in controls could represent early neoplastic changes or normal homeostatic process of apoptosis occurring in lung tissue to get rid of mutant cells. At the same time, mutations detected in patients might represent a non-invasive easily accessible way for early cancer detection. Follow up of individuals with important cancer mutations is necessary to clarify the significance of these mutations in both healthy individuals and cancer patients.

Keywords: exhaled breath condensate, lung cancer, mutations, next generation sequencing

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Authors: A. M. Gadanya, M. S. Sule

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Effect of oral administration of Gadagi tea on some antioxidant enzymes was assessed in healthy male albino rats. The rats were grouped and administered with standard doses of the 3 types of Gadagi tea i.e. Sak, Sada and Magani for a period of four weeks. Animals that were not administered with the tea constituted the control group. At the end of fourth week, the animals were sacrificed and their serum superoxide dismutase (SOD), glutathione reductase (GR) and catalase (CAT) activities were determined. The activities of the enzymes were also determined in the brain, liver, kidney and intestine homogenates of the rats. Mean SOD activity in brain of rats orally administered with “sada” was found to be significantly higher (P < 0.05) than that of the control group. Mean CAT activity in the intestine of rats orally administered with “magani” was found to be significantly higher (P < 0.05) than that of the control group and the experimental groups of Sak and Sada at standard dose level. Thus, all the “Gadagi” tea preparations studied at standard dose level could stimulate antioxidant enzymes, especially SOD in brain and CAT in intestine (by Sada) and CAT in intestine (by Magani).

Keywords: “Gadagi” tea, superoxide dismutase, catalase, glutathione reductase

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Authors: Joseph Bamidele Minari

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The anti-jaundice properties of the methanolic extract of Carica papaya leaves on albino rat was evaluated. In order to achieve this, the phytochemical screening of the extract was carried out, and carbon tetrachloride (CCl4) (i.p) was injected into albino rats to induce jaundice. The rats were simultaneously given oral doses of 20 mg/kg, 40 mg/kg, 60 mg/kg, 80 mg/kg and 100 mg/kg (p.o) of methanolic extract of C. papaya. The effects of these extract on total bilirubin concentration, liver ALT AST, GGT activities of the jaundice-induced rats were studied after seven days period of the experiment. Administration of CCl4 alone to the rats significantly increased (p<0.05) total bilirubin concentration while the activities of ALT, AST, and GGT in the liver when compared to controls which received distilled water (p.o) was significantly lower (p<0.05). Simultaneous treatment of CCl4 injection, and oral administration of different doses of the C. papaya extract significantly reduced (p<0.05) total bilirubin concentration in the serum while the liver ALT AST, GGT activities significantly increased (p < 0.05). However, the lowest significant reduction (p<0.05) of bilirubin concentration was observed with simultaneous administration of 60mg/kg of the extract on the rats. This study suggests that the extract of C. papaya leaves possess the phytochemicals that have anti-jaundice properties.

Keywords: carica papaya, jaundice, herbal medicine, liver, rat

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Authors: Divya Pathak, James Sloane

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Surgical treatment of midface fractures should ideally occur within two weeks of injury, after which bony healing and consolidation make the repair more difficult for the operating surgeon. The oral and maxillofacial unit at the Royal Surrey Hospital is the tertiary referral center for maxillofacial trauma from five regional hospitals. This is a complete audit cycle of midface trauma referrals managed over a one year period. The standard set was that clinical assessment of the midface fracture would take place in a consultant led outpatient clinic within 7 days, and when indicated, surgical fixation would occur within 10 days of referral. Retrospective data was collected over one year (01/11/2018 - 31/12/2019). Three key changes were implemented: an IT referral mailbox, standardization of an on-call trauma table, and creation of a trauma theatre list. Re-audit was carried out over six months completing the cycle. 283 midface fracture referrals were received, of which 22 patients needed surgical fixation. The average time from referral to outpatient follow-up improved from 14.5 days to 8.3 days, and time from referral to surgery improved from 21.5 days to 11.6 days. Changes implemented in this audit significantly improved patient prioritization to appropriate outpatient clinics and shortened time to surgical intervention.

Keywords: maxillofacial trauma, midface trauma, oral and maxillofacial surgery, surgery fixation

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Authors: Kamsiah Jaarin, Yusof Kamisah, Faizah Othman Nurul Akmal Muhammad, Zakiah Jubri, Qodriyah Mohd Saad, Srijit Das

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Forty (40) normotensive adult male Sprague-Dawley rats aged three months weighing 180-200 g were divided into 4 groups with 10 rats per group: (1) normotensive control; (2) hypertensive rats; (3) hypertensive rats treated with Nigella sativa (2.5 ml/kg/day); and (4) hypertensive rats treated with nicardipine (5 mg/kg/day). After acclimatization, the hypertensive rats of the group 2, 3 and 4 were induced to be hypertensive by giving NW–nitro-L-arginine methyl ester (L-NAME; 30 mg/kg/day) in their drinking water for consecutive 7 days. After one week, rats in the group 3 were given a daily oral dose of 2.5 ml/kg/day of Nigella sativa (NS) by oral gavage. Rats in the group 4 were given nicardipine (5 mg/kg/day) via oral gavages. All rats in this study received L-NAME continuously throughout the treatment duration. The blood pressure will be measured pre-treatment and weekly for 8 weeks using power lab. Blood was taken before and at the end of study for measurement of nitric oxide. At the end of 8 weeks, the rats are sacrificed and descending thoracic aorta was disserted for measurement of vascular reactivity, and intracellular adhesion molecules (ICAM-1) and vascular cell adhesion molecules (VCAM-1). Nigella sativa reduced both systolic and diastolic BP compared to control and L-name group. The BP lowering effect of NS was comparable to nicardipine a calcium antagonist. The blood pressure lowering effect of NS was accompanied with an increasing relaxation response to nitroprusside and acetylcholine and reducing vasoconstriction response to epinephrine. L-NAME and nicardipine on the other hand, reduced plasma nitric oxide concentration. In contrast, NS increased NO concentration. However, Nigella sativa had no significant effect on aortic VCAM- 1 and ICAM-1 expression. In conclusion; Nigella sativa oil reduces both systolic and diastolic blood pressure in L-NAME treated rats. The antihypertensive effect of NS was comparable to nicardipine. The BP lowering effect may be mediated via stimulating nitric oxide release from vascular endothelium.

Keywords: Nigella sativa, ICAM, VCAM, blood pressure, vascular reactivity

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Authors: Armenia Nazar, Sally M. J. Anggelya, Rose Dinda

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Hypertension prevalence in Indonesian has increased from time to time since 2013, especially in women. This cross-sectional analysis study was made to observe the incidence of hypertension on the reproductive women (20-49 years old) with several risk factors who use contraceptive pills. Data was collected from June - October 2016 in the Andalas Public Health Center, East Padang District, Indonesia. An amount of 167 respondents who were taken using consecutive sampling technique were participate in this study. Data of social demography, contraceptive used, duration of use, hypertension risk factors (age, family history, central obesity, body mass index, physical activity, and stress) were collected and analyzed statistically using Chi-Square analysis. Significant was taken at p < 0.05. Results showed that the woman with contraceptive pill was tent to get hypertension (OR = 3,90 and p < 0,001). In addition, woman with a family history OR of 6,77 (p = 0,09), mild physical activity OR of 3,67 (p = 0,33), moderate physical activity OR of 3,33 (p = 0,16), and stressed OR of 5.11 (p = 0.18). These indicated that the contraceptive pill user is 3.9 times more risk to develop hypertension than non-users, especially one with a family history of hypertension. Other risk factors were not associated with hypertension risk in these sex productive women.

Keywords: hypertension, oral contraceptive, sex productive woman, risk factors

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Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

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Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

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Authors: Andhiani Sharfina Arnellya, Mochammad Indra Permana, Dika Pramita Destiani, Ellin Febrina

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Health Research Data, Ministry of Health of Indonesia in 2007, showed coronary heart disease (CHD) or coronary artery disease (CAD) was the third leading cause of death in Indonesia after hypertension and stroke with 7.2% incidence rate. Antiplatelet is one of the important therapy in management of patients with CHD. In addition to therapeutic effect on patients, quality of life is one aspect of another assessment to see the success of antiplatelet therapy. The purpose of this study was to determine the quality of life of patients on oral antiplatelet therapy in outpatient cardiac department Dr. Hasan Sadikin central general hospital, Bandung, Indonesia. This research is a cross sectional by collecting data through quality of life questionnaire of patients which performed prospectively as primary data and secondary data from medical record of patients. The results of this study showed that 54.3% of patients had a good quality of life, 45% had a moderate quality of life, and 0.7% had a poor quality of life. There are no significant differences in quality of life-based on age, gender, diagnosis, and duration of drug use.

Keywords: antiplatelet, quality of life, coronary artery disease, coronary heart disease

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Authors: Naseem Fatima, A. N. Srivastava, Tasleem Raza, Vijay Kumar

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Introduction: Carcinoma gallbladder is third most common gastrointestinal lethal disease with the highest incidence and mortality rate among women in Northern India. Scientists have found several risk factors that make a person more likely to develop gallbladder cancer; among these risk factors, deregulation of miRNAs has been demonstrated to be one of the most crucial factors. The changes in the expression of specific miRNA genes result in the control of inflammation, cell cycle regulation, stress response, proliferation, differentiation, apoptosis and invasion thus mediate the process in tumorgenesis. The aim of this study was to investigate the role of MiRNA-335 and may as a molecular marker in early detection of gallbladder cancer in suspected cases. Material and Methods: A total of 20 consecutive patients with gallbladder cancer aged between 30-75 years were registered for the study. Total RNA was extracted from tissue by using the mirVANA MiRNA isolation Kit according to the manufacturer’s protocol. The MiRNA- 335 and U6 snRNA-specific cDNA were reverse-transcribed from total RNA using Taqman microRNA reverse-transcription kit according to the manufacturer’s protocol. TaqMan MiRNA probes hsa-miR-335 and Taqman Master Mix without AmpEase UNG, Individual real-time PCR assays were performed in a 20 μL reaction volume on a Real-Time PCR system (Applied Biosystems StepOnePlus™) to detect MiRNA-335 expression in tissue. Relative quantification of target MiRNA expression was evaluated using the comparative cycle threshold (CT) method. The correlation was done in between cycle threshold (CT Value) of target MiRNA in gallbladder cancer with respect to non-cancerous Cholelithiasis gallbladder. Each sample was examined in triplicate. The Newman-Keuls Multiple Comparison Test was used to determine the expression of miR-335. Results: MiRNA335 was found to be significantly downregulated in the gallbladder cancer tissue (P<0.001), when compared with non-cancerous Cholelithiasis gallbladder cases. Out of 20 cases, 75% showed reduced expression of MiRNA335, were at last stage of disease with low overall survival rate and remaining 25% were showed up-regulated expression of MiRNA335 with high survival rate. Conclusion: The present study showed that reduced expression of MiRNA335 is associated with the advancement of the disease, and its deregulation may provide important clues to understanding it as a prognostic marker and opportunities for future research.

Keywords: carcinoma gallbladder, downregulation, MiRNA-335, RT-PCR assay

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Authors: T. Almutairi, K. Naudi, N. Nairn, X. Ju, B. Eng, J. Whitters, A. Ayoub

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Purpose: At present Cone Beam Computed Tomography (CBCT) imaging does not record dental morphology accurately due to the scattering produced by metallic restorations and the reported magnification. The aim of this pilot study is the development and validation of a new method for the replacement of the distorted dentition of CBCT scans with the dental image captured by the digital intraoral camera. Materials and Method: Six dried skulls with orthodontics brackets on the teeth were used in this study. Three intra-oral markers made of dental stone were constructed which were attached to orthodontics brackets. The skulls were CBCT scanned, and occlusal surface was captured using TRIOS® 3D intraoral scanner. Marker based and surface based registrations were performed to fuse the digital intra-oral scan(IOS) into the CBCT models. This produced a new composite digital model of the skull and dentition. The skulls were scanned again using the commercially accurate Laser Faro® arm to produce the 'gold standard' model for the assessment of the accuracy of the developed method. The accuracy of the method was assessed by measuring the distance between the occlusal surfaces of the new composite model and the 'gold standard' 3D model of the skull and teeth. The procedure was repeated a week apart to measure the reproducibility of the method. Results: The results showed no statistically significant difference between the measurements on the first and second occasions. The absolute mean distance between the new composite model and the laser model ranged between 0.11 mm to 0.20 mm. Conclusion: The dentition of the CBCT can be accurately replaced with the dental image captured by the intra-oral scanner to create a composite model. This method will improve the accuracy of orthognathic surgical prediction planning, with the final goal of the fabrication of a physical occlusal wafer without to guide orthognathic surgery and eliminate the need for dental impression.

Keywords: orthognathic surgery, superimposition, models, cone beam computed tomography

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Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

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Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

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Authors: Arghavan Tonkaboni, Shamsolmolouk Najafi, Mohmmad Taghi Kiani, Mehrzad Gholampour, Touraj Goli

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Introduction: Recurrent aphthous stomatitis (RAS) is a multifactorial recurrent oral lesion; which is an autoimmune disease. TH1 cytokines are the most important etiological factors. Autoimmune thyroid disease (ATD) is one of the most common autoimmune diseases and generally coexists with other autoimmune diseases. This study assessed the prevalence of thyroid disease in patients with recurrent aphthous stomatitis. Materials and Methods: This case control study assessed 100 known RAS patients who were diagnosed clinically by oral medicine specialists; venous blood samples were analyzed for thyroid stimulating hormone (TSH), free triiodothyronine (fT3), total thyroxine (fT4), thyroglobulin, anti-thyroid peroxidase antibody (anti-TPO) and anti-thyroglobulin antibody (anti-TG) levels. Results: Fifty patients with RAS aged between 18-42 years (28.5±5.8) and 50 healthy volunteers aged 19-45 years (27.3±5.4) participated. In RAS patients, fT3 and TSH levels were significantly higher (P=0.031, P=0.706); however, fT4 level was lower in the RAS group (P=0.447). Anti TG and anti-TPO levels were significantly higher in the RAS group (P=0.008, P=0.067). Conclusion: Our study showed that ATD prevalence was significantly higher in RAS patients. Based on this study, we recommend assessment of thyroid hormones and antibodies in RAS patients.

Keywords: recurrent aphthous stomatitis, thyroid antibodies, thyroid hormone, thyroid autoimmune disease

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Authors: Aulina R. Rahmi, Farid Yuristiawan, Annisa Ibifadillah, Ummu H. Amri, Hidayati Gunawan

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Glass ionomer cement is one of the filling material that often used on the field of dentistry because it is relatively less expensive and mostly available. Restoration materials could undergo changes in their clinical properties such as changes in roughness of the restoration`s surface. An increase of surface roughness accelerates bacterial colonization and plaque maturation. In the oral cavity, GIC was exposed to various substances, such as toothpaste, an oral care product used during toothbrushing. One of the popular toothpaste is whitening toothpaste. Abrasive and chemical agents such as hydrogen peroxide in whitening toothpaste could increase the surface roughness of restorative materials. Objective: To determine the differences on the surface roughness of glass ionomer cement that was brushed with whitening and conventional toothpaste. Method: This study was done using experimental laboratory method with pre and post test design. There were 36 samples which were divided into 2 groups. The first group was brushed with whitening toothpaste and the second group was brushed with conventional toothpaste, each for 2 minutes. Surface roughness value of the specimens was measured by using Roughness Tester test. Result: The data was analyzed by using independent t-test and the result of this study showed there was a significant difference between the surface of glass ionomer cement which was brushed with whitening and conventional toothpaste (p=0,000). Conclusion: Glass ionomer cement that was brushed with whitening toothpaste produced more roughness than conventional toothpaste.

Keywords: glass ionomer cement, surface roughness, toothpaste, roughness tester

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Authors: Alireza Barari

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Physical activity and diet are factors that influence the body's structure. The purpose of this study was to compare the effects of four weeks of resistance training, and glutamine supplement consumption on growth hormone (GH), and Insulin-like growth factor 1 (IGF-1) Axis. 40 amateur male bodybuilders, participated in this study. They were randomly divided into four equal groups, Resistance (R), Glutamine (G), Resistance with Glutamine (RG), and Control (C). The R group was assigned to a four week resistance training program, three times/week, three sets of 10 exercises with 6-10 repetitions, at the 80-95% 1RM (One Repetition Maximum), with 120 seconds rest between sets), G group is consuming l-glutamine (0.1 g/kg^-1/day^-1), RG group resistance training with consuming L-glutamine, and C group continued their normal lifestyle without exercise training. GH, IGF1, IGFBP-III plasma levels were measured before and after the protocol. One-way ANOVA indicated significant change in GH, IGF, and IGFBP-III between the four groups, and the Tukey test demonstrated significant increase in GH, IGF1, IGFBP-III plasma levels in R, and RG group. Based upon these findings, we concluded that resistance training at 80-95% 1RM intensity, and resistance training along with oral glutamine shows significantly increase secretion of GH, IGF-1, and IGFBP-III in amateur males, but the addition of oral glutamine to the exercise program did not show significant difference in GH, IGF-1, and IGFBP-III.

Keywords: strength, glutamine, growth hormone, insulin-like growth factor 1

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Authors: Taleb Lotfi, Benarbia Maheidine, Allam Hamza, Boutira Fatima, Boukerche Abdelbaki

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Introduction and purpose of the study: This is a retrospective single-center study with an analytical aim to determine the prognostic factors for relapse in patients treated with radiotherapy after total laryngectomy with lymph node dissection for laryngeal cancer at the Emir Abdelkader cancer center in Oran (Algeria). Material and methods: During the study period from January 2014 to December 2018, eighty-nine patients (n=89) with squamous cell carcinoma of the larynx were treated with postoperative radiotherapy. Relapse-free survival was studied in the univariate analysis according to pre-treatment criteria using Kaplan-Meier survival curves. We performed a univariate analysis to identify relapse factors. Statistically significant factors have been studied in the multifactorial analysis according to the Cox model. Results and statistical analysis: The average age was 62.7 years (40-86 years). It was a squamous cell carcinoma in all cases. Postoperatively, the tumor was classified as pT3 and pT4 in 93.3% of patients. Histological lymph node involvement was found in 36 cases (40.4%), with capsule rupture in 39% of cases, while the limits of surgical excision were microscopically infiltrated in 11 patients (12.3%). Chemotherapy concomitant with radiotherapy was used in 67.4% of patients. With a median follow-up of 57 months (23 to 104 months), the probabilities of relapse-free survival and five-year overall survival are 71.2% and 72.4%, respectively. The factors correlated with a high risk of relapse were locally advanced tumor stage pT4 (p=0.001), tumor site in case of subglottic extension (p=0.0003), infiltrated surgical limits R1 (p=0.001), l lymph node involvement (p=0.002), particularly in the event of lymph node capsular rupture (p=0.0003) as well as the time between surgery and adjuvant radiotherapy (p=0.001). However, in the subgroup analysis, the major prognostic factors for disease-free survival were subglottic tumor extension (p=0.001) and time from surgery to adjuvant radiotherapy (p=0.005). Conclusion: Combined surgery and postoperative radiation therapy are effective treatment modalities in the management of laryngeal cancer. Close cooperation of the entire cervicofacial oncology team is essential, expressed during a multidisciplinary consultation meeting, with the need to respect the time between surgery and radiotherapy.

Keywords: laryngeal cancer, laryngectomy, postoperative radiotherapy, survival

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Authors: Muhammad Asif Syed, Mirza Amir Baig

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Background: Pakistan is one of the two remaining polio-endemic countries, posing a significant public health challenge for global polio eradication due to failure to interrupt polio transmission. Country specific seroprevalence studies help in the evaluation of immunization program performance, the susceptibility of population against polio virus and identification of existing level of immunity with factors that affect seroconversion of the oral polio vaccine (OPV). The objective of the study was to find out factors associated with seroconversion of the OPV among children 6-59 months in Pakistan. Methods: A Hospital based cross-sectional serosurvey was undertaken in May-June 2015 at District Mirpurkhas, Sindh-Pakistan. Total 180 children aged 6–59 months were selected by using systematic random sampling from Muhammad Medical College Hospital, Mirpurkhas. Demographic, vaccination history and risk factors information were collected from the parents/guardian. Blood sample was collected and tested for the detection of poliovirus IgG antibodies by using ELISA Kit. The IgG titer <10 IU/ml, 50 to <150 IU/ml and >150 IU/ml was defined as negative, weak positive and positive immunity respectively. Pearson Chi-square test was used to determine the difference in seroprevalence in univariate analysis. Results: A total of 180 subjects were enrolled mean age was 23 months (7 -59 months). Off these 160 (89%) children were well and 18 (10%) partially protected against polio virus. Two (1.1%) children had no protection against polio virus as they had <10 IU/ml poliovirus IgG antibodies titer. Both negative cases belong from the female gender, age group 12-23 months, urban area and BMI <50 percentile. There was a difference between normal and the wasting children; it did attain statistical significance (χ2= 35.5, p=0.00). The difference in seroconversion was also observed in relation to the gender (χ2=6.23, p=0.04), duration of breast feeding (χ2=18.6, p=0.04), history of diarrheal disease before polio vaccine administration (χ2=7.7, p=0.02), and stunting (χ2= 114, p=0.00). Conclusion: This study demonstrated that near 90% children achieve seroconversion of OPV and well protected against polio virus. There is an urgent need to focus on factors like duration of breast feeding, diarrheal diseases and malnutrition (acute and chronic) among the children as an immunization strategy.

Keywords: seroconversion, oral polio vaccine, Polio, Pakistan

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Authors: Omar Nouri, Wafa Mnejja, Nejla Fourati, Fatma Dhouib, Wicem Siala, Ilhem Charfeddine, Afef Khanfir, Jamel Daoud

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Background and objective: Induction chemotherapy (IC) followed by concomitant chemo radiotherapy with intensity modulated radiation (IMRT) technique is actually the recommended treatment modality for locally advanced nasopharyngeal carcinomas (NPC). The aim of this study was to evaluate the prognostic factors predicting loco regional relapse with this new treatment protocol. Patients and methods: A retrospective study of 52 patients with NPC treated between June 2016 and July 2019. All patients received IC according to the protocol of the Head and Neck Radiotherapy Oncology Group (Gortec) NPC 2006 (3 TPF courses) followed by concomitant chemo radiotherapy with weekly cisplatin (40 mg / m2). Patients received IMRT with integrated simultaneous boost (SIB) of 33 daily fractions at a dose of 69.96 Gy for high-risk volume, 60 Gy for intermediate risk volume and 54 Gy for low-risk volume. Median age was 49 years (19-69) with a sex ratio of 3.3. Forty five tumors (86.5%) were classified as stages III - IV according to the 2017 UICC TNM classification. Loco regional relapse (LRR) was defined as a local and/or regional progression that occurs at least 6 months after the end of treatment. Survival analysis was performed according to Kaplan-Meier method and Log-rank test was used to compare anatomy clinical and therapeutic factors that may influence loco regional free survival (LRFS). Results: After a median follow up of 42 months, 6 patients (11.5%) experienced LRR. A metastatic relapse was also noted for 3 of these patients (50%). Target volumes coverage was optimal for all patient with LRR. Four relapses (66.6%) were in high-risk target volume and two (33.3%) were borderline. Three years LRFS was 85,9%. Four factors predicted loco regional relapses: histologic type other than undifferentiated (UCNT) (p=0.027), a macroscopic pre chemotherapy tumor volume exceeding 100 cm³ (p=0.005), a reduction in IC doses exceeding 20% (p=0.016) and a total cumulative cisplatin dose less than 380 mg/m² (p=0.0.34). TNM classification and response to IC did not impact loco regional relapses. Conclusion: For nasopharyngeal carcinoma, tumors with initial high volume and/or histologic type other than UCNT, have a higher risk of loco regional relapse. Therefore, they require a more aggressive therapeutic approaches and a suitable monitoring protocol.

Keywords: loco regional relapse, modulation intensity radiotherapy, nasopharyngeal carcinoma, prognostic factors

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Authors: J. Szpor, K. Witczak, M. Storman, A. Orchel, D. Hodorowicz-Zaniewska, K. Okoń, A. Klimkowska

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Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease. In comparison to fine needle aspiration (FNA), CNB provides more architectural information allowing for the evaluation of prognostic and predictive factors for breast cancer, including histological grade—one of three prognostic factors used to calculate the Nottingham Prognostic Index. Several studies have previously described the concordance rate between CNB and surgical excision specimen in determination of histological grade (HG). The concordance rate previously ascribed to overall grade varies widely across literature, ranging from 59-91%. The aim of this study is to see how the data looks like in material at authors’ institution and are the results as compared to those described in previous literature. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. Both materials were evaluated for the determination of histological grade (scale from 1 to 3). HG was assessed only in core needle biopsies containing at least 10 well preserved HPF with invasive tumor. The degree of concordance between CNB and surgical excision specimen for the determination of tumor grade was assessed by Cohen’s kappa coefficient. The level of agreement between core needle biopsy and surgical resection specimen for overall histologic grading was 73% (113 of 155 cases). CNB correctly predicted the grade of the surgical excision specimen in 21 cases for grade 1 tumors (Kappa coefficient κ = 0.525 95% CI (0.3634; 0.6818), 52 cases for grade 2 (Kappa coefficient κ = 0.5652 95% CI (0.458; 0.667) and 40 cases for stage 3 tumors (Kappa coefficient κ = 0.6154 95% CI (0.4862; 0.7309). The highest level of agreement was observed in grade 3 malignancies. In 9 of 42 (21%) discordant cases, the grade was higher in the CNB than in the surgical excision. This composed 6% of the overall discordance. These results correspond to the noted in the literature, showing that underestimation occurs more frequently than overestimation. This study shows that authors’ institution’s histologic grading of CNBs and surgical excisions shows a fairly good correlation and is consistent with findings in previous reports. Despite the inevitable limitations of CNB, CNB is an effective method for diagnosing breast cancer and managing treatment options. Assessment of tumour grade by CNB is useful for the planning of treatment, so in authors’ opinion it is worthy to implement it in daily practice.

Keywords: breast cancer, concordance, core needle biopsy, histological grade

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Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar

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Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.

Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics

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Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah

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Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.

Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate

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Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: Jeong Woo Kang, MiYoung Baek, Ki-Suk Kim, Kwang-Jick Lee, ByungJae So

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Introduction: A fast, easy and sensitive detection method was developed and validated by liquid chromatography tandem mass spectrometry for the determination of marbofloxacin in pig plasma which was further applied to study the pharmacokinetics of marbofloxacin. Materials and Methods: The plasma sample (500 μL) was mixed with 1.5 ml of 0.1% formic acid in MeCN to precipitate plasma proteins. After shaking for 20 min, The mixture was centrifuged at 5,000 × g for 30 min. It was dried under a nitrogen flow at 50℃. 500 μL aliquot of the sample was injected into the LC-MS/MS system. Chromatographic analysis was carried out mobile phase gradient consisting 0.1% formic acid in D.W. (A) and 0.1% formic acid in MeCN (B) with C18 reverse phase column. Mass spectrometry was performed using the positive ion mode and the selected ion monitoring (MRM). Results and Conclusions: The method validation was performed in the sample matrix. Good linearities (R2>0.999) were observed and the quantified average recoveries of marbofloxacin were 87 - 92% at level of 10 ng g-1 -100 ng g-1. The percent of coefficient of variation (CV) for the described method was less than 10 % over the range of concentrations studied. The limits of detection (LOD) and quantification (LOQ) were 2 and 5 ng g-1, respectively. This method has also been applied successfully to pharmacokinetic analysis of marbofloxacin after intravenous (IV), intramuscular (IM) and oral administration (PO). The mean peak plasma concentration (Cmax) was 2,597 ng g-1at 0.25 h, 2,587 ng g-1at 0.44 h and 2,355 ng g-1at 1.58 h for IV, IM and PO, respectively. The area under the plasma concentration-time curve (AUC0–t) was 24.8, 29.0 and 25.2 h μg/mL for IV, IM and PO, respectively. The elimination half-life (T1/2) was 8.6, 13.1 and 9.5 for IV, IM and PO, respectively. Bioavailability (F) of the marbofloxacin in pig was 117 and 101 % for IM and PO, respectively. Based on these result, marbofloxacin does not have any obstacles as therapeutics to develop the oral formulations such as tablets and capsules.

Keywords: marbofloxacin, LC-MS/MS, pharmacokinetics, chromatographic

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Authors: Dalia O. Saleha, Gehad A. Abdel Jaleela, Sally W. Al-Awdana

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Diabetes mellitus (DM) is known to exacerbate cerebral ischemic injury. The present study aimed to investigate the anti-oxidant and anti-inflammatory effects of oral supplementation of melatonin (MLN) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in streptozotocin (STZ)-induced hyperglycemic rats. Hyperglycemia was induced by a single injection of STZ (55mg/kg; i.p.), six weeks later the cerebral injury was induced by MCAO/Re. Twenty-four hours after the MCAO/Re the MLN (10 mg/kg) was injected for 14 consecutive days. Results of the present study revealed that MCAO/Re in STZ-induced hyperglycemia in rats causes an increase in the oxidative stress biomarkers; it increased brain lipid peroxidation (measured as malondialdehyde; MDA) and brain level of nitric oxide (NO). Moreover, MCAO/Reproduces a prominent increase in the brain inflammatory markers viz. interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis nuclear factor-alpha (TNF-α). Oral treatment of MCAO/Re in STZ-induced hyperglycemic rats with MLN (10 mg/kg) for two weeks restored the brain levels of MDA, GSH, NO, IL-6, IL-1β and the TNF-α. MLN succeeded to suppress the exacerbation of damage in the brain of hyperglycemic rats. These results suggest that daily intake of MLN attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-oxidant and anti-inflammatory effects in the brain.

Keywords: melatonin, brain injury, cerebral ischemia/reperfusion, hyperglycemia, rats

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Authors: Anik Barua, Rabiul Hossain, Labonno Barua, Rashadul Hossain, Nurul Absar

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Background: Globally, the burden of cancer is increasing consistently. Modern cancer therapies include lots of toxicity in the non-targeted organs reducing the life expectancy of the patients. Hence, scientists are trying to seek noble compounds from natural sources to treat cancer. Objectives: The objectives of the present study are to evaluate the phytochemicals, in vitro antioxidants, and in vivo and in silico anticancer study of various solvent fractions of Tinospora cordifolia (Willd.). Methodology: In this experiment, standard quantitative and qualitative assay methods were used to analyze the phytochemicals. The antioxidant activity was measured using the DPPH and ABTS scavenging methods. The in vivo antitumor activity is evaluated against Ehrlich ascites carcinoma (EAC) cell bearing in Swiss albino mice. In-silico ADME/T and molecular docking study were performed to assess the potential of stated phytochemicals against Transcription Factor STAT3b/DNA Complex of adenocarcinoma. Findings: Phytochemical screening confirmed the presence of flavonoids, alkaloids, glycosides, tannins, and carbohydrates. A significant amount of phenolic (20.19±0.3 mg/g GAE) and flavonoids (9.46±0.18 mg/g GAE) were found in methanolic extract in quantitative screening. Tinospora cordifolia methanolic extract showed promising DPPH and ABTS scavenging activity with the IC50 value of 1222.99 µg/mL and 1534.34 µg/mL, respectively, which was concentration dependent. In vivo anticancer activity in EAC cell-bearing mice showed significant (P < 0.05) percent inhibition of cell growth (60.12±1.22) was found at the highest dose compared with standard drug 5-Fluorouracil (81.18±1.28). Forty-two phytochemicals exhibit notable pharmacokinetics properties and passed drug-likeness screening tests in silico. In molecular docking study, (25S)-3Beta-acetoxy-5-alpha-22-beta-spirost-9(11)-en-12-beta-ol showed docking score (-8.5 kJ/mol) with significant non-bonding interactions with target enzyme. Conclusions: The results were found to be significant and confirmed that the methanolic extract of Tinospora cordifolia has remarkable antitumor activity with antioxidant potential. The Tinospora cordifolia methanolic extract may be considered a potent anticancer agent for advanced research.

Keywords: anticancer, antioxidant, Tinospora cordifolia, EAC cell

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Authors: Wenjun Zhang, Yunqing Du, Steven W. Cranford, Ming L. Wang

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The beginning of 21st century has witnessed new advancements in the design and use of new materials for biosensing applications, from nano to macro, protein to tissue. Traditional analytical methods lack a complete toolset to describe the complexities introduced by living systems, pathological relations, discrete hierarchical materials, cross-phase interactions, and structure-property dependencies. Materiomics – via systematic molecular dynamics (MD) simulation – can provide structure-process-property relations by using a materials science approach linking mechanisms across scales and enables oriented biosensor design. With this approach, DNA biosensors can be utilized to detect disease biomarkers present in individuals’ breath such as acetone for diabetes. Our wireless sensor array based on single-stranded DNA (ssDNA)-decorated single-walled carbon nanotubes (SWNT) has successfully detected trace amount of various chemicals in vapor differentiated by pattern recognition. Here, we present how MD simulation can revolutionize the way of design and screening of DNA aptamers for targeting biomarkers related to oral diseases and oral health monitoring. It demonstrates great potential to be utilized to build a library of DNDA sequences for reliable detection of several biomarkers of one specific disease, and as well provides a new methodology of creating, designing, and applying of biosensors.

Keywords: biosensor, DNA, biomarker, molecular dynamics simulation

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Authors: Gayatri Swarnakar

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Paramphistomiasis and fascioliasis diseases have been prevalent due to presence of trematode parasites in the rumen and liver of domestic buffalo (Bubalus bubalis) in Udaipur, India. The trematode parasites such as Paramphistomum cervi, Gastrothylax crumenifer, Cotylophoron cotylophorum, Orthocoelium scoliocoelium, Fasciola hepatica and Fasciola gigantica were collected from infected rumen and liver of the freshly slaughtered buffaloes (Bubalus bubalis) at local zoo abattoir in Udaipur. Live trematodes were washed in normal saline, fixed in 0.2M cacodylate fixative, post fixed in osmium tetraoxide, dehydrated, dried, coated with gold sputter and observed under scanning electronic microscope (SEM). The surface tegument of Paramphistomum cervi was spineless with transverse folds, discontinuous with ridges and grooves. Two types of sensory papillae such as knob like and button shaped were also observed. The oral opening of Cotylophoron cotylophorum was surrounded by wrinkled and ridged tegument which formed concentric elevated rings. Tegument of Cotylophoron cotylophorum in acetabulum region was observed to be rough and bee-comb like structure. Genital sucker of this worm was surrounded by a tyre- shaped elevation of the tegument. Orthocoelium scoliocoelium showed circular and concentric rings of tegumental folds around the oral sucker. Genital pore had knob like papillae with radial tegumental folds. Surface topography of Fasciola gigantica and Fasciola hepatica were found to be rough due to occurrence of different types of spines, three types of sensory papillae, transverse folds and grooves. Oral and ventral suckers were spineless and covered with thick rims of transverse folds. Genital pore showed small scattered spines. Present research work would provide knowledge for ultrastructural characteristics of trematode parasites for chemotherapeutic measures and help us to evolve suitable strategy for the eradication of trematode parasites from the domestic buffalo (Bubalus bubalis).

Keywords: Domestic buffalo, tegument, trematode parasites, ultrastructure

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Authors: Atul Srivastava, D. V. Gowda

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Enterotoxigenic Escherichia coli (ETEC) infection is one of the major causes contributing to the development of diarrhoea in adults and children in developing countries. To date, no preventive/treatment strategy showed promising results, which could be due to the lack of potent vaccines, and/or due to the development of resistance of ETEC to antibiotics. Therefore, in the present investigation, a novel porous Sodium Alginate (SA) tablet formulation loaded with F4 fimbriae antigen was developed and tested for efficacy against ETEC infections in piglet models. Pre-compression parameters of the powder mixes and post compression parameters of tablets have been evaluated and results were found to be satisfactory. Loading of F4 fimbrial antigens in to the tablets was achieved by inducing pores in the tablets via the sublimation of camphor followed by incubation with purified F4 fimbriae. The loaded tablets have been coated with Eudragit L100 to protect the F4 fimbriae from (a) highly acidic gastric environment; (b) proteolytic cleavage by pepsin; and (c) to promote subsequent release in the intestine. Evaluation of developed F4 fimbrial tablets in a Pig model demonstrated induction of mucosal immunity, and a significant reduction of F4+ E. coli in faeces. Therefore, F4 fimbriae loaded porous tablets could be a novel oral vaccination candidate to induce mucosal and systemic immunity against ETEC infections.

Keywords: porous tablets, sublimation, f4 fimbriae, eudragit l100, vaccination

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Authors: Mathew O. Ayoola, Foluke Aderemi, Tunde E. Lawal, Opeyemi Oladejo, Micheal A. Abiola

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Food animals reared for meat require transportation during their life cycle. The transportation procedures could initiate stressors capable of disrupting the physiological homeostasis. Such stressors associated with transportation may include; loading and unloading, crowding, environmental temperature, fear, vehicle motion/vibration, feed / water deprivation, and length of travel. This may cause oxidative stress and damage to excess free radicals or reactive oxygen species (ROS). In recent years, the application of natural products as a substitute for synthetic electrolytes and tranquilizers as anti-stress agents during the transportation is yet under investigation. Sweet orange, a predominant fruit in humid tropics, has been reported to have a good content of vitamin C (Ascorbic acid). Vitamin C, which is an active ingredient in orange juice, plays a major role in the biosynthesis of Corticosterone, a hormone that enhances energy supply during transportation and heat stress. Ninety-six, 15weeks, Isa brown pullets were allotted to four (4) oral treatments; sterile water (T1), synthetic vit C (T2), 30ml orange/liter of water (T3), 50ml orange/1 liter (T4). Physiological parameters; body temperature (BTC), rectal temperature (RTC), respiratory rate (RR), and panting rate (PR) were measured pre and post-transportation. The birds were transported with a specialized vehicle for a distance of 50km at a speed of 60 km/hr. The average environmental THI and within the vehicle was 81.8 and 74.6, respectively, and the average wind speed was 11km/hr. Treatments and periods had a significant (p>0.05) effect on all the physiological parameters investigated. Birds on T1 are significantly (p<0.05) different as compared to T2, T3, and T4. Values recorded post-transportation are significantly (p<0.05) higher as compared to pre-transportation for all parameters. In conclusion, this study showed that transportation as a stressor can affect the physiological homeostasis of pullets. Oral supplementation of electrolytes or tranquilizers is essential as an anti-stress during transportation. The application of the organic product in form of sweet orange could serve as a suitable alternative for the synthetic vitamin C.

Keywords: physiological, pullets, sweet orange, transportation stress, and vitamin C

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