Cytotoxicity Activity and Druggability Studies of Sigmasterol Isolated from Marine Sponge Dysidea avara Against Oral Epithelial Cancer Cell (KB/C152) and T-Lymphocytic Leukemia Cell Line (Jurkat/ E6-1)

Background: Marine sponge is a rich natural resource of many pharmacological compounds and various bioactive anticancer agents are derived from marine organisms like sponges. Methods: studying the anticancer activity and Drug ability of marine sponge Dysidea avara using Cell lines oral epithelial cancer cell (KB/C152) and T-lymphocytic leukemia cell line (Jurkat/ E6-1). Marine sponge was collected from Persian Gulf. Several analytical techniques have been used to obtain and recognize stigmasterol, including column chromatography, thin layer chromatography, and gas chromatography-mass spectrometry. The PASS Prediction Activity was used to investigate the apoptosis-inducing effect of stigmasterol. The cytotoxic activity of stigmasterol was examined using yellow tetrazolium salt XTT (sodium 2, 3,-bis (2methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium) assay. The stigmasterol were docked within the protein tyrosine kinase (PTKs) (PDB code: 1t46) and epidermal growth factor receptor (EGFRK) (PDB code: 1M17). Also, the pharmacological characteristics of stigmasterol were predicted using PerADME, SwissADME, and Molinspi ration tools. Apoptosis-inducing effect of stigmasterol indicate the stigmasterol in terms of the possibility of apoptosis in cells. Results: The apoptosis inducement results of known stigmasterol were determined by PASS on-line prediction. The compound exhibit potent cytotoxic properties against KB/C152 cell compared to Jurkat/ E6-1 cell. The stigmasterol showed the cytotoxicity effects on KB/C152 and HUT78 with IC50 ranges of 81.18 and 103.03 μg/ml, respectively. Molecular docking showed that, stigmasterol bound stably to the active sites of the protein tyrosine kinase (PTKs) (PDB code: 1t46) and epidermal growth factor receptor (EGFRK) (PDB code: 1M17). Conclusion: The compound showed desirable pharmacokinetic properties (ADME). This provided direct evidence of how a prospective anti-cancer agent can be stigmasterol. The preclinical studies paved the way for a potential new compound of anti-cancer.     

Professional practices in the management of adrenal insufficiency in two tertiary referral hospitals (Tunis,Tunisia)

Background: Adrenal insufficiency (AI) is a rare and life-threatening disease. Glucocorticoid replacement therapy and patient education are crucial. Few is known about physician practice in this topic. Aims: To describe physician practice in the management of AI and to identify the associated factors. Methods: the physicians, all grades and specialties, from two university hospitals in Tunis, were invited to respond to a paper-based 16- multiple choice item-questionnaire about the management of AI and the prevention of acute AI. Each question was scored 1 if correct or 0 if incorrect. The global score was calculated by adding the score of the first 15 questions. Results: 200 physicians responded to the questionnaire, sex ratio: 0.47, mean age: 29.0 ± 5.8 years (24 - 60). The overall rate of correct answers was 59.6%. The rate of correct responses was good for the type of replacement therapy (92%), the lifelong duration of treatment (88%), the symptoms of overtreatment (73.5%), the type of diet indicated (77%), and the necessity of special measures during the peri operative period (100%). However, the rate of correct responses was low for the half-life of hydrocortisone (12.5%), biological signs suggesting acute AI (17.5%), situations during which an increase in the dose of glucocorticoid is required (26.5%) and the risks of intermittent fasting (2%). Endocrinology specialty and overall medical specialties were independently associated with a better global score. Conclusion: physician practice in the management of AI need to be improved.     

Satisfaction des patients diabétiques surla qualité des services de santé ambulatoires

Aim: To assess the degree of satisfaction of diabetic patients with health care services and to determine the factors that influence it. Methods: It was a cross sectional study conducted in 2018 among diabetic outpatients of the department of endocrinology of the university hospital La Rabta. Patients general characteristics were noted. Each patient responded to a questionnaire, asked orally, in Tunisian dialect, by two physicians, about health care services including 20 questions grouped into three items. Each question was scored from 1 to 4 according to the degree of satisfaction. The global score as well as the scores of the items were calculated by adding the scores of the corresponding questions. Results: 150 diabetic patients responded to the questionnaire; mean age: 58.9±12.2 years [18-88], sex-ratio: 0.51.Cronbach coefficient was 0.78. The overall score was 62.2±6.5 [46-80]. Ninety-seven patients (64.7%) had a score ≥60. The item concerning ‘human contact and communication’ was considered good in 98% of cases. The item concerning ‘premises, cleanliness, comfort and safety’ was considered intermediate in 64% of cases. Patients were very satisfied with the accessibility of the department inside the hospital (76.7%), the attitude of the agents during the administrative formalities (74%) and particularly the behaviour of the doctor (96%). However, they were dissatisfied with the noise (72%) and overcrowding (67.4%) of the waiting room. There were no statistically significant associations between the overall score and the studied data. Conclusion: The diabetic patients were overall satisfied with the provided services. Actions must be taken to reduce overcrowding and long waiting times..     

A diffuse large B‐cell thyroid lymphoma presented as a compressive goiter in a young woman with no evidence of Hashimoto's thyroiditis

Thyroid lymphoma should be suspected in case of rapid enlargement of the thyroid gland even in a young patient with no history of Hashimoto thyroiditis. The confirmation is based on histopathology and immunohistochemistry.     

Immunosuppression and oxidative stress induced by subchronic exposure to carbosulfan in rat spleen: immunomodulatory and antioxidant role of N-acetylcysteine

The present study was designed to determine the immunosuppressive effects of carbosulfan (CB) and their relationship with an increased formation of reactive oxygen species in rat. Further, we aimed to evaluate the protective effects of N-acetyl-cysteine (NAC) against immunopathological changes induced by CB. Carbosulfan (25?mg/kg) and NAC (2?g/l) were given daily to rats during 30 days, via oral gavage and drinking water, respectively. Cell-mediated immune function, cytokines production, biomarkers of cell redox state maintenance, lipid peroxidation and the activities of antioxidant enzymes were measured in the spleen. Our data showed an increase in WBC percent (28.42%), a reduction in spleen CD8 T-lymphocytes (?85.63%) and a decrease in immunosuppressive cytokines production such as INF-gamma and IL-4. There was a switch from Th1-type to Th2-type cytokines with an unbalance toward anti-inflammatory cytokines. Moreover, a significant decrease in reduced glutathione (?71.68%) and total thiols (?39.81%) levels were observed in treated rats. Conversely, malondialdehyde level in spleen was increased (?42.3%), while glutathione-S-transferase, glutathione peroxidase, superoxide dismutase and catalase activities were depleted. Our results suggest that subchronic CB administration affects cellular enzyme and non-enzyme-mediated antioxidant defense systems and promotes immunotoxicity in rat. On the other hand, our data showed protective effects of NAC. Indeed, there was a recovery of oxidative stress markers and cytokines production. The use of NAC, in our study, as a therapeutic agent showed interesting results against CB toxicity.     

Evaluation of the Cytotoxic Activity of Crocin and Safranal,Constituents of Saffron,in Oral Squamous Cell Carcinoma (KB Cell Line)

Crocin and safranal are active ingredients in the saffron. Some studies have demonstrated antitumor activities of saffron ingredients. The aim of this study was to evaluate cytotoxic effects of crocin and safranal in oral squamous cell carcinoma (KB cells) and NIH 3T3 cell line as nonmalignant cells. The cells were incubated with crocin and safranal at 37°C for 24, 48, and 72 h, and cell viability was quantitated by MTT assay. Apoptotic cells, cell cycle distribution, and sub-G1 fraction were determined using propidium iodide staining of DNA fragmentation by flow cytometry. Crocin (0.05–4 mM) and safranal (0.2–3.2 mM) significantly inhibited the growth of KB cells (the inhibitory growth effects of all concentrations for both were >50% after 72 h), while they had less inhibitory effects on NIH 3T3 cells viability. The IC₅₀ values of crocin and safranal against NIH 3T3 cells after 72 h were determined as 2.8 and 0.3 mM, respectively. Crocin and safranal induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in the toxicity of crocin and safranal. Apoptotic effects of crocin and safranal in tumor cells were more than normal cells. Neither crocin nor safranal affected the cell cycle progression. Crocin and safranal exerted apoptotic effects in KB cell line.     

GingerenoneA overcomes dexamethasone resistance by activating apoptosis and inhibiting cell proliferation in pediatric T-ALL cells

Plant-based combination strategies have been widely considered in cancer therapy to attenuate chemotherapeutics side effects. The anti-leukemic effect of the whole ginger extract was previously portrayed by our team, and the current study is centered around the cytotoxicity and mechanism of action of a phenolic subsidiary of ginger, GingerenoneA, on pediatric acute lymphoblastic leukemia. GingernoneA imposed, dose-dependently, inhibitory effects on the viability of T and B leukemia cell lines confirmed by MTT assays. Resistance to Dexamethasone, a mostly used chemotherapeutic in acute lymphoblastic leukemia treatments, was overcome by GingernoneA. A synergistic effect of Dexamethasone and GingrenoneA on T leukemia cell lines and patient primary cells was confirmed. Annexin-V/PI and acridine orange/ethidium bromide staining illustrated dose-dependent apoptosis in CCRF-CEM cells developed by GingerenoneA. The intrinsic and extrinsic apoptosis induction and antiproliferative attribution of GingerenoneA were validated by western blot and qPCR. Despite the supposed loss of function in CCRF-CEM cells, TP53 showed increased expression levels and functional activity upon treatment with GingernoneA. Bioinformatic studies revealed the conceivable impact of GingerenoneA on the reactivity of mutant P53 through its binding to Cys124. Our findings may provide novel strategies for therapeutic intervention to ameliorate pALL outcomes.