Search results for: cytotoxic drugs

Authors: Alami Ilyass, Loubna Kharchoufa, Elachouri Mostafa

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The two great realms of living diversity are cultural and biological. Today, both are being lost at an alarming rate. Of all the Earth’s biological diversity, plant kingdom is of high significance, and most essential to human welfare, in fact, medicinal plants are extensively exploited for countless purposes. Among these multiple uses, medicinal plants are the most important source of medicine for humankind healthcare and well being. In recent years there has been a great surge of public interest in the use of herbs and plants. Some scientists have viewed this phenomenon as a modern “herbal renaissance”. The importance of plants as medicines in developed and developing countries has recently been acknowledged by the United Nations (UN). However, to date fewer than 5% of the approximately 250,000 species of higher plants have been exhaustively studied for their potential pharmacological activity. A number of drugs from ethnobotanical leads have provided significant milestones in Western medicine. Despite this success, pharmacognosy research on Moroccan flora needs more studies aimed at the exploration of their therapeutic potential. A major weakness is the absence of strong funding agencies in the country, and a real national drug discovery program. Moreover, the lack of the coordination between different universities and research institutions leads, in most cases, to a waste of time, money and efforts of many researchers. In this work, we focus our attention on research into traditional indigenous medicinal plants in Morocco. Three parts constitute the head lines of this work: In the first one, we take up Moroccan biodiversity matter, the second part is devoted principally to the state of research into medicinal plants by Moroccan scholars and the last one is consecrated to the debate of factors which handicap the progress of research on phytomedicine in Morocco. The objectives of the present study are twofold: first, to highlight the state of the medicinal plants researches in Morocco. Second goal is to assess and correlate the levels of knowledge of the local flora to the research on medicinal plants to attempt to build capacity for research within Moroccan Scientific community at rate of developing country.

Keywords: Morocco, medicinal plants, ethnobotanical, pharmacognosy, phytomedicine

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Authors: Evelyn Osehontue Uroro, Richard Bright, Jing Yang Quek, Krasimir Vasilev

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Bacterial infections have been a challenge both in the public and private sectors. The colonization of bacteria often occurs in medical devices such as catheters, heart valves, respirators, and orthopaedic implants. When biomedical devices are inserted into patients, the deposition of macromolecules such as fibrinogen and immunoglobin on their surfaces makes it easier for them to be prone to bacteria colonization leading to the formation of biofilms. The formation of biofilms on medical devices has led to a series of device-related infections which are usually difficult to eradicate and sometimes cause the death of patients. These infections require surgical replacements along with prolonged antibiotic therapy, which would incur additional health costs. It is, therefore, necessary to prevent device-related infections by inhibiting the formation of biofilms using intelligent technology. Antibiotic resistance of bacteria is also a major threat due to overuse. Different antimicrobial agents have been applied to microbial infections. They include conventional antibiotics like rifampicin. The use of conventional antibiotics like rifampicin has raised concerns as some have been found to have hepatic and nephrotoxic effects due to overuse. Hence, there is also a need for proper delivery of these antibiotics. Different techniques have been developed to encapsulate and slowly release antimicrobial agents, thus reducing host cytotoxicity. Examples of delivery systems are solid lipid nanoparticles, hydrogels, micelles, and polymeric nanoparticles. The different ways by which drugs are released from polymeric nanoparticles include diffusion-based release, elution-based release, and chemical/stimuli-responsive release. Polymeric nanoparticles have gained a lot of research interest as they are basically made from biodegradable polymers. An example of such a biodegradable polymer is polycaprolactone (PCL). PCL degrades slowly by hydrolysis but is often sensitive and responsive to stimuli like enzymes to release encapsulants for antimicrobial therapy. This study presents the synthesis of PCL nanoparticles loaded with rifampicin and the on-demand release of rifampicin for treating staphylococcus aureus infections.

Keywords: enzyme, Staphylococcus aureus, PCL, rifampicin

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Authors: Gabriela Rivadeneyra-Romero, Claudia del C. Gutierrez Torres, Sergio A. Martinez-Delgadillo, Victor X. Mendoza-Escamilla, Alejandro Alonzo-Garcia

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Ultrasonic degradation is currently being used in sonochemical reactors to degrade pollutant compounds from aqueous media, as emerging contaminants (e.g. pharmaceuticals, drugs and personal care products.) because they can produce possible ecological impacts on the environment. For this reason, it is important to develop appropriate water and wastewater treatments able to reduce pollution and increase reuse. Pollutants such as textile dyes, aromatic and phenolic compounds, cholorobenzene, bisphenol-A and carboxylic acid and other organic pollutants, can be removed from wastewaters by sonochemical oxidation. The effect on the removal of pollutants depends on the type of the ultrasonic frequency used; however, not much studies have been done related to the behavior of the fluid into the sonoreactors operated at different ultrasonic frequencies. Based on the above, it is necessary to study the hydrodynamic behavior of the liquid generated by the ultrasonic irradiation to design efficient sonoreactors to reduce treatment times and costs. In this work, it was studied the hydrodynamic behavior of the fluid in sonochemical reactors at different frequencies (250 kHz, 500 kHz and 1000 kHz). The performances of the sonoreactors at those frequencies were simulated using computational fluid dynamics (CFD). Due to there is great sound speed gradient between piezoelectric and fluid, k-e models were used. Piezoelectric was defined as a vibration surface, to evaluate the different frequencies effect on the fluid into sonochemical reactor. Structured hexahedral cells were used to mesh the computational liquid domain, and fine triangular cells were used to mesh the piezoelectric transducers. Unsteady state conditions were used in the solver. Estimation of the dissipation rate, flow field velocities, Reynolds stress and turbulent quantities were evaluated by CFD and 2D-PIV measurements. Test results show that there is no necessary correlation between an increase of the ultrasonic frequency and the pollutant degradation, moreover, the reactor geometry and power density are important factors that should be considered in the sonochemical reactor design.

Keywords: CFD, reactor, ultrasound, wastewater

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Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli

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This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Cherif Y., Ghariani R., Derbal S., Farhati S., Ben Dahmen F., Abdallah M.

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Introduction: Tuberculosis (TBC) is a frequent infection and is still a major public health problem in Tunisia. The aim of this work is to focus on diagnostic and therapeutic characteristics of TBC in patients referred to our internal medicine department. Patients and Methods: The study was retrospective and descriptive of a cohort of consecutive cases treated from January 2016 to December 2019, collecting patients with latent or patent TBC. Twenty-eight medical records of adults diagnosed with TBC were reviewed. Results: Twenty-eight patients, including 18 women and 10 men, were diagnosed with TBC. Their mean age is 48 years (range: 22-78 years). Five patients have a medical history of diabetes mellitus, 1 patient was followed for systemic lupus erythematosus treated with corticosteroids and immunosuppressant drugs, and another was treated with corticosteroids for Mac Duffy syndrome. The TBC is latent in 12 cases and patent in 16 cases. The most common symptoms were fever and weight loss and were found in 10 cases, a cough in 2 cases, sputum in 3 cases, lymph nodes in 4 cases, erythema nodosum in 2 cases, and neurological signs in 3 cases. Lymphopenia is noticed in 3 cases and a biological inflammatory syndrome in 18 of the cases. The purified protein derivate reaction was positive in 17 cases, anergic in 3 cases, negative in 5 cases, and not done in 3 cases. The acid-fast bacilli stain culture was strongly positive in one patient. The histopathological study was conclusive in 11 patients and showed granulomatosis with caseous necrosis. TBC was pulmonary in 7 patients, lymph node in 7 cases, peritoneal in 7 cases, digestive in 1 case, neuromeningeal in 3 cases, and thyroïd in 1 case. Seven patients had multifocal TBC. All the patients received anti-tuberculosis treatment with a mean duration of 8 months with no failure or relapse with an average follow-up time of 10.58 months. Conclusion: Diagnosis and management of TBC remain essential to avoid serious complications. The survey is necessary to ensure timely detection and treatment of infected adults to decrease its incidence. The best treatment remains preventive through vaccination and improving social and economic conditions.

Keywords: tuberculosis, infection, autoimmune disease, granulomatosis

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Authors: Stoyanka Georgieva Vladeva, Elena Kirilova Kirilova, Nikola Kirilov Kirilov

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Summary: WHO (World Health Organization) recommends the elder people a certain amount of regular physical activity in order to prevent some of the health issues. Postmenopausal osteoporosis is one of the chronic diseases which requires the maintaining of regular physical activity. The regular activity combined with an adequate medical treatment greatly improves the quality of life of the patient. Objectives: Assessment of the effect of the regular physical activity recommended by WHO on the quality of life in patients with postmenopausal osteoporosis. Material and methods: For the period of one year 68 female patients treated with Denosumab have been monitored. The bone density has been measured with the DEXA method in accordance to the T-score. No patients having any oncologic diseases and secondary osteoporosis have been included in the study. The subjects have been divided into groups by their age. The first group – women aged under 65 years (27 subjects) and the second group – women aged over 65 years (41 subjects). All patients have been advised to maintain regular physical activity included in the recommendations of the WHO in accordance with the age and the disease. The quality of life has been assessed in the beginning and at the end of the one-year period using the SF 36V2 questionnaire. Results: Only 31% of the subjects have engaged into regular increased physical activities for the whole period. Among them are mostly patients of the second group (aged over 65 years, 71%). The women from the both groups who were engaging into regular activities for this one-year period all experience an improvement of the quality of life. These results show that older patients understand the necessity of the physical activity for their health. The comparison of the output data to the scales of physical activity, durability, body pain, vitality, social activity and emotional stability has found an improvement at the end of the period in all patients. The osteodensitometry showed general improvement of the T-score. Patients with additional visits to their rheumatologist have better results. Conclusion: Combination of regular physical activity in accordance to the recommendations of WHO and medical treatment including anti-osteoporotic drugs improves the quality of life of women with postmenopausal osteoporosis.

Keywords: elderly patients, osteoporosis, physical activity, quality of life

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Authors: Shilu Deepa Thomas, P. Jayaprakash, Dorota Łazewska, Katarzyna Kieć-Kononowicz, B. Sadek

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A large body of evidence suggests the involvement of cognitive impairment, increased levels of inflammation and oxidative stress in the pathogenesis of autism spectrum disorder (ASD). ASD commonly coexists with psychiatric conditions like anxiety and cognitive challenges, and individuals with ASD exhibit significant levels of inflammation and immune system dysregulation. Previous Studies have identified elevated levels of pro-inflammatory markers such as IL-1β, IL-6, IL-2 and TNF-α, particularly in young children with ASD. The current therapeutic options for ASD show limited effectiveness, signifying the importance of exploring an efficient drugs to address the core symptoms. The role of histamine H3 receptors (H3Rs) in memory and the prospective role of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., ASD, is well-accepted. Hence, the effects of chronic systemic administration of H3R antagonist E159 on autistic-like repetitive behaviors, social deficits, memory and anxiety parameters, as well as neuroinflammation in Black and Tan BRachyury (BTBR) mice, were evaluated using Y maze, Barnes maze, self-grooming, open field and three chamber social test. E159 (2.5, 5 and 10 mg/kg, i.p.) dose-dependently ameliorated repetitive and compulsive behaviors by reducing the increased time spent in self-grooming and improved reduced spontaneous alternation in BTBR mice. Moreover, treatment with E159 attenuated disturbed anxiety levels and social deficits in tested male BTBR mice. Furthermore, E159 attenuated oxidative stress by significantly increasing GSH, CAT, and SOD and decreasing the increased levels of MDA in the cerebellum as well as the hippocampus. In addition, E159 decreased the elevated levels of proinflammatory cytokines (tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and IL-6). The observed results show that H3R antagonists like E159 may represent a promising novel pharmacological strategy for the future treatment of ASD.

Keywords: histamine H3 receptors, antagonist E159, autism, behaviors, mice

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Authors: Napasri Suwanajote

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The purposes of this research were to analyze and evaluate successful factors in OTOP production process for the developing of learning center on OTOP production process based on Sufficiency Economic Philosophy for sustainable life quality. The research has been designed as a qualitative study to gather information from 30 OTOP producers in Bangkontee District, Samudsongkram Province. They were all interviewed on 3 main parts. Part 1 was about the production process including 1) production, 2) product development, 3) the community strength, 4) marketing possibility, and 5) product quality. Part 2 evaluated appropriate successful factors including 1) the analysis of the successful factors, 2) evaluate the strategy based on Sufficiency Economic Philosophy, and 3) the model of learning center on OTOP production process based on Sufficiency Economic Philosophy for sustainable life quality. The results showed that the production did not affect the environment with potential in continuing standard quality production. They used the raw materials in the country. On the aspect of product and community strength in the past 1 year, it was found that there was no appropriate packaging showing product identity according to global market standard. They needed the training on packaging especially for food and drink products. On the aspect of product quality and product specification, it was found that the products were certified by the local OTOP standard. There should be a responsible organization to help the uncertified producers pass the standard. However, there was a problem on food contamination which was hazardous to the consumers. The producers should cooperate with the government sector or educational institutes involving with food processing to reach FDA standard. The results from small group discussion showed that the community expected high education and better standard living. Some problems reported by the community included informal debt and drugs in the community. There were 8 steps in developing the model of learning center on OTOP production process based on Sufficiency Economic Philosophy for sustainable life quality.

Keywords: production process, OTOP, sufficiency economic philosophy, language choice

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Authors: Dong-Gi Lee, Suyeon Cha, Yong-Sun Bahn

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Sterol lipid is essential for cell membrane structure in eukaryotic cells. In mammalian cells, sterol regulatory element binding proteins (SREBPs) act as principal regulators of cellular cholesterol which is essential for proper cell membrane fluidity and structure. SREBP and sterol regulation are related to levels of cellular oxygen because it is a major substrate for sterol synthesis. Upon cellular sterol and oxygen levels are depleted, SREBP is translocated to the Golgi where it undergoes proteolytic cleavage of N terminus, then it travels to the nucleus to play a role as transcription factor. In yeast cells, synthesis of ergosterol is also highly oxygen consumptive, and Sre1 is a transcription factor known to play a central role in adaptation to growth under low oxygen condition and sterol homeostasis in Cryptococcus neoformans. In this study, we observed phenotypes in other strains of Cryptococcus species by constructing hob1Δ and sre1Δ mutants to confirm whether the functions of both genes are conserved in most serotypes. As a result, hob1Δ showed no noticeable phenotype under treatment of antifungal drugs and most environmental stresses in R265 (C. gattii) and XL280 (C. neoformans), suggesting that Hob1 is related to sterol regulation only in H99 (serotype A). On the other hand, the function of Sre1 was found to be conserved in most serotypes. Furthermore, mating experiment of hob1Δ or sre1Δ showed dramatic defects in serotype A (H99) and D (XL280). It revealed that Hob1 and Sre1 related to mating ability in Cryptococcus species, especially cell fusion efficiency. In conclusion, HOB1 and SRE1 play crucial role in regulating sterol-homeostasis and differentiation in C. neoformans, moreover, Hob1 is specific gene in Cryptococcus neoformans. It suggests that Hob1 is considered as potent factor-targeted new safety antifungal drug.

Keywords: cryptococcus neoformans, Hob1, Sre1, sterol regulatory element binding proteins

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Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

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Authors: Wenjie Wu, Peng Cheng, Zehua Zhang, Fei Luo, Feng Wu, Min Zhong, Jianzhong Xu

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Background: There has been limited research into the therapeutic efficacy of rapid diagnosis of spinal tuberculosis complicated with pulmonary tuberculosis. We attempted to discover whether the utilization of a DNA microarray assay to detect multidrug-resistant spinal tuberculosis complicated with pulmonary tuberculosis can improve clinical outcomes. Methods: A prospective study was conducted from February 2006 to September 2015. One hundred and forty-three consecutive culture–confirmed, clinically and imaging diagnosed MDR-TB patients with spinal tuberculosis complicated by pulmonary tuberculosis were enrolled into the study. The initial time to treatment for MDR-TB, the method of infection control, radiological indicators of spinal tubercular infectious foci, culture conversion, and adverse drug reactions were compared with the standard culture methods. Results: Of the total of 143 MDR-TB patients, 68 (47.6%) were diagnosed by conventional culture methods and 75 (52.4%) following the implementation of detection using the DNA microarray. Patients in the microarray group began rational use of the second-line drugs schedule more speedily than sufferers in the culture group (17.3 vs. 74.1 days). Among patients were admitted to a general tuberculosis ward, those from the microarray group spent less time in the ward than those from the culture group (7.8 vs. 49.2 days). In those patients with six months follow-up (n=134), patients in the microarray group had a higher rate of sputum negativity conversion at six months (89% vs. 73%). In the microarray group, the rate of drug adverse reactions was significantly lower (22.2% vs. 67.7%). At the same time, they had a more obvious reduction of the area with spinal tuberculous lesions in radiological examinations (77% vs. 108%). Conclusions: The application of the CapitalBio™ DNA Microarray assay caused noteworthy clinical advances including an earlier time to begin MDR-TB treatment, increased sputum culture conversion, improved infection control measures and better radiographical results

Keywords: tuberculosis, multidrug-resistant, tuberculous spondylitis, DNA microarray, clinical outcomes

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Authors: Wadha Alqahtani

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In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

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Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

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Authors: Ben Main Piotr Ozieranski

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State government spending on pharmaceuticals stands at 1 trillion USD globally, promoting criticism of the pharmaceutical industry's monetization of drug efficacy, product cost overvaluation, and health injustice. This paper elucidates the mechanisms behind a state-institutional response to this problem through the sociological lens of the strategic relational approach to state power. To do so, 30 expert interviews, legal and policy documents are drawn on to explain how state elites in New Zealand have successfully contested a 30-year “pharmaceutical spending containment policy”. Proceeding from Jessop's notion of strategic “selectivity”, encompassing analyses of the enabling features of state actors' ability to harness state structures, a theoretical explanation is advanced. First, a strategic context is described that consists of dynamics around pharmaceutical dealmaking between the state bureaucracy, pharmaceutical pricing strategies (and their effects), and the industry. Centrally, the pricing strategy of "bundling" -deals for packages of drugs that combine older and newer patented products- reflect how state managers have instigated an “incentivization game” that is played by state and industry actors, including HTA professionals, over pharmaceutical products (both current and in development). Second, a protective context is described that is comprised of successive legislative-judicial responses to the strategic context and characterized by the regulation and the societalisation of commercial law. Third, within the policy, the achievement of increased pharmaceutical coverage (pharmaceutical “mix”) alongside contained spending is conceptualized as a state defence of a "social profit". As such, in contrast to scholarly expectations that political and economic cultures of neo-liberalism drive pharmaceutical policy-making processes, New Zealand's state elites' approach is shown to be antipathetic to neo-liberals within an overall capitalist economy. The paper contributes an analysis of state pricing strategies and how they are embedded in state regulatory structures. Additionally, through an analysis of the interconnections of state power and pharmaceutical value Abrahams's neo-liberal corporate bias model for pharmaceutical policy analysis is problematised.

Keywords: pharmaceutical governance, pharmaceutical bureaucracy, pricing strategies, state power, value theory

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Authors: Shivankar Agrawal, Sunil Kumar Deshmukh, Colin Barrow, Alok Adholeya

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A variety of genetic and environmental factors cause various cosmetics and dermatological problems. There are already claimed drugs available in market for treating these problems. However, the challenge remains in finding more potent, environmental friendly, causing minimal side effects and economical cosmeceuticals. This leads to an increased demand for natural cosmeceutical products in the last few decades. Plant derived ingredients are limited because plants either contain toxic metabolites, grow too slow or seasonal harvesting is a problem. To identify new bioactive cosmetics ingredients of marine microbial bioresource, we screened 35 marine fungi isolated from marine samples collected from Andaman Island and west coast of India. Fungal crude extracts were investigated for their antityrosinase, antioxidant and antibacterial activities for the purpose of identifying anti-aging, skin-whitening and anti-acne biomolecule with the potential in cosmetics. In the tyrosinase inhibition and 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays, two fungal extracts, including “P2”, Talaromyces stipitatus and “D4”, Aspergillus terreus showed high inhibitory activity at 1mg/mL for tyrosinase inhibition and 0.5mg/mL for DPPH scavenging. The in vitro antimicrobial activity was investigated by the agar well diffusion method. In the tyrosinase inhibition assay, 8 extracts showed significant antibacterial activity against bacteria causing skin and wound infection in humans. In the course of systematic screening program for bioactive marine fungi, strain “D5” was found to be most potent strain with MIC value of 1mg/mL, which was morphologically identified as Simplicillium lamellicola. The effects of the most active crude extracts against their susceptible test microorganisms were also investigated by SEM analysis. Further investigations will focus on purification and characterization major active components responsible for these activities.

Keywords: antioxidant, antimicrobial activity, tyrosinase, cosmeceuticals, marine fungi

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Authors: Zakaria Baka, Halima Alem

Abstract:

Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.

Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques

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Authors: A. Aslihan Gokaltun, Martin L. Yarmush, Ayse Asatekin, O. Berk Usta

Abstract:

Poly(dimethylsiloxane) (PDMS) is one of the most widely used materials in the fabrication of microfluidic devices. It is easily patterned and can replicate features down to nanometers. Its flexibility, gas permeability that allows oxygenation, and low cost also drive its wide adoption. However, a major drawback of PDMS is its hydrophobicity and fast hydrophobic recovery after surface hydrophilization. This results in significant non-specific adsorption of proteins as well as small hydrophobic molecules such as therapeutic drugs limiting the utility of PDMS in biomedical microfluidic circuitry. While silicon, glass, and thermoplastics have been used, they come with problems of their own such as rigidity, high cost, and special tooling needs, which limit their use to a smaller user base. Many strategies to alleviate these common problems with PDMS are lack of general practical applicability, or have limited shelf lives in terms of the modifications they achieve. This restricts large scale implementation and adoption by industrial and research communities. Accordingly, we aim to tailor biocompatible PDMS surfaces by developing a simple and one step bulk modification approach with novel smart materials to reduce non-specific molecular adsorption and to stabilize long-term cell analysis with PDMS substrates. Smart polymers that blended with PDMS during device manufacture, spontaneously segregate to surfaces when in contact with aqueous solutions and create a < 1 nm layer that reduces non-specific adsorption of organic and biomolecules. Our methods are fully compatible with existing PDMS device manufacture protocols without any additional processing steps. We have demonstrated that our modified PDMS microfluidic system is effective at blocking the adsorption of proteins while retaining the viability of primary rat hepatocytes and preserving the biocompatibility, oxygen permeability, and transparency of the material. We expect this work will enable the development of fouling-resistant biomedical materials from microfluidics to hospital surfaces and tubing.

Keywords: cell culture, microfluidics, non-specific protein adsorption, PDMS, smart polymers

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Authors: Simone F. Medeiros, Jessica M. Fonseca, Gizelda M. Alves, Danilo M. Santos, Sérgio P. Campana-Filho, Amilton M. Santos

Abstract:

Stimuli responsive and biocompatible hydrogel nanoparticles have gained special attention as systems for potential applications in controlled release of drugs to improve their therapeutic efficacy while minimizing side effects. In this work, novel solid dispersions based on thermo- and pH-responsive poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate) hydrogel nanoparticles embedded in chitosan matrices were prepared via spray drying for controlled release of ketoprofen. Firstly, the hydrogel nanoparticles containing ketoprofen were prepared via precipitation polymerization and their stimuli-responsive behavior, thermal properties, chemical composition, encapsulation efficiency and morphology were characterized. Then, hydrogel nanoparticles with different particles size were embedded into chitosan matrices via spray-drying. Scanning electron microscopy (SEM) analyses were performed to investigate the particles size, dispersity and morphology. Finally, ketoprofen release profiles were studied as a function of pH and temperature. Chitosan/poly(NVCL-co-IA-co-EGDMA)-ketoprofen microparticles presented spherical shape, rough surface and pronounced agglomeration, indicating that hydrogels nanoparticles loaded with ketoprofen modified the surface of chitosan matrix. The maximum encapsulation efficiency of ketoprofen into hydrogel nanoparticles was 57.8% and the electrostatic interactions between amino groups from chitosan and carboxylic groups from hydrogel nanoparticles were able to control ketoprofen release. The hydrogel nanoparticles themselves were capable to retard the release of ketoprofen-loaded until 48h of in vitro release tests, while their incorporation into chitosan matrix achieved a maximum percentage of drug release of 45%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 10:7, and 69%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 5:2.

Keywords: hydrogel nanoparticles, poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate), chitosan, ketoprofen, spray-drying

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Authors: H. Haseena Banu, D. Karthick, R. Stalin, E. Nandha Kumar, T. P. Sachidanandam, P. Shanthi

Abstract:

Background of the study: Type 2 diabetes is emerging as the predominant metabolic disorder in the world among adults characterized mainly by the resistance of the insulin sensitive tissues towards insulin followed by the decrease in the insulin secretion. The treatment for this disease usually involves treatment with oral synthetic drugs which are known to cause several side effects. Therefore, identification of new biomarkers as therapeutic target is the need of the hour. miRNAs are small, non–protein-coding RNAs that negatively regulate gene expression by promoting degradation and/or inhibit the translation of target mRNAs and have emerged as biomarkers in predicting diabetes mellitus. Objective of the study: To elucidate the therapeutic role of gallic acid in modulating the alterations in glucose metabolism induced by miRNAs 194 and 135a in Type 2 diabetic rats. Materials and Methods: T2D was induced in rats by feeding them with a high fat diet for 2 weeks followed by intraperitoneal injection of 35 mg/kg/body weight (b.wt.) of streptozotocin. Microarrays were used to assess the expression of miRNAs in control, diabetic and gallic acid treated rats. Gene expression studies were carried out by RT PCR analysis. Results: Forty one miRNAs were differentially expressed in Type 2 diabetic rats. Among these, the expression of miRNA 194 was significantly decreased whereas miRNA 135a was significantly increased in Type 2 diabetic rats. The glucose metabolism was also altered significantly in skeletal muscle of Type 2 diabetic rats. Conclusion: T2D is associated with alterations in the expression of miRNAs in skeletal muscle. Both these miRNAs 194 and 135a play an important role in glucose metabolism in skeletal muscle of diabetic rats. Gallic acid effectively ameliorated the alterations in glucose metabolism. Hence, both these miRNAs can serve as biomarkers and therapeutic targets in diabetes mellitus. The study also establishes the role of gallic acid as therapeutic agent. Acknowledgment: The financial assistance provided in the form of ICMR women scientist by ICMR DHR INDIA is gratefully acknowledged here.

Keywords: gallic acid, high fat diet, type 2 diabetes mellitus, miRNAs

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Authors: F. Alaa Ali, S. A. Sherein Abdelgayed, S. Osama. EL-Tawil, M. Adel Bakeer

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Tartrazine is an organic azo dyes food additive widely used in foods, drugs, and cosmetics. The present study aimed to investigate the toxic effects of tartrazine on kidneys and liver biomarkers in addition to the investigation of oxidative stress and change of histopathological structure of liver and kidneys in 30 male rats. Tartrazine was orally administrated daily at dose 200 mg/ kg bw (1/ 10 LD₅₀) for sixty days. Serum and tissue samples were collected at the end of the experiment to investigate the underlying mechanism of tartrazine through assessment oxidative stress (Glutathione (GSH), Superoxide dismutase (SOD) and malondialdehyde (MDA) and biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total protein and Urea). Liver and kidneys tissue were collected and preserved in 10% formalin for histopathological examination. The obtained values were statistically analyzed by one way analysis of variance (ANOVA) followed by multiple comparison test. Biochemical analysis revealed that tartrazine induced significant increase in serum ALT, AST, total protein, urea level compared to control group. Tartrazine showed significant decrease in liver GSH and SOD where their values when compared to control group. Tartrazine induced increase in liver MDA compared to control group. Histopathology of the liver showed diffuse vacuolar degeneration in hepatic parenchyma, the portal area showed sever changes sever in hepatoportal blood vessels and in the bile ducts. The kidneys showed degenerated tubules at the cortex together with mononuclear leucocytes inflammatory cells infiltration. There is perivascular edema with inflammatory cell infiltration surrounding the congested and hyalinized vascular wall of blood vessel. The present study indicates that the subchronic effects of tartrazine have a toxic effect on the liver and kidneys together with induction of oxidative stress by formation of free radicals. Therefore, people should avoid the hazards of consuming tartrazine.

Keywords: albino rats, tartrazine, toxicity, pathology

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Authors: Rayhana Begum, Manju Sharma

Abstract:

Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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Authors: Njabulo Ncube, Elena Kulinskaya, Nicholas Steel, Dmitry Pshezhetskiy

Abstract:

Life expectancy in the United Kingdom (UK) has been near constant since 2010, particularly for the individuals of 65 years and older. This trend has been also noted in several other countries. This slowdown in the increase of life expectancy was concurrent with the increase in the number of deaths caused by non-communicable diseases. Of particular concern is the world-wide exponential increase in the number of diabetes related deaths. Previous studies have reported increased mortality hazards among diabetics compared to non-diabetics, and on the differing effects of antidiabetic drugs on mortality hazards. This study aimed to estimate the all-cause mortality hazards and related life expectancies among type 2 diabetes (T2DM) patients in the UK using the time-variant Gompertz-Cox model with frailty. The study also aimed to understand the major causes of the change in life expectancy growth in the last decade. A total of 221 182 (30.8% T2DM, 57.6% Males) individuals aged 50 years and above, born between 1930 and 1960, inclusive, and diagnosed between 2000 and 2016, were selected from The Health Improvement Network (THIN) database of the UK primary care data and followed up to 31 December 2016. About 13.4% of participants died during the follow-up period. The overall all-cause mortality hazard ratio of T2DM compared to non-diabetic controls was 1.467 (1.381-1.558) and 1.38 (1.307-1.457) when diagnosed between 50 to 59 years and 60 to 74 years, respectively. The estimated life expectancies among T2DM individuals without further comorbidities diagnosed at the age of 60 years were 2.43 (1930-1939 birth cohort), 2.53 (1940-1949 birth cohort) and 3.28 (1950-1960 birth cohort) years less than those of non-diabetic controls. However, the 1950-1960 birth cohort had a steeper hazard function compared to the 1940-1949 birth cohort for both T2DM and non-diabetic individuals. In conclusion, mortality hazards for people with T2DM continue to be higher than for non-diabetics. The steeper mortality hazard slope for the 1950-1960 birth cohort might indicate the sub-population contributing to a slowdown in the growth of the life expectancy.

Keywords: T2DM, Gompetz-Cox model with frailty, all-cause mortality, life expectancy

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Authors: M. Osibemhe, I. O. Onoagbe

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Diabetes mellitus is a common disease that has no known cure. The available orthodox drugs used for its management have one or more disadvantages. This study investigated the potency of aqueous and ethanol extracts of Strophanthus hispidus (SH) stem bark in the management of diabetes mellitus. Glucose concentration and lipid profile parameters of normal and streptozotocin-induced diabetic rats were monitored for 12weeks. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin (55 mg/kg). Male rats (wistar strain) numbering 30 were randomly selected into six groups of five rats each. Groups 1 and 6 served as normal and diabetic control respectively and received distilled water for 12weeks. Groups 2 and 3 were normal rats treated orally with the aid of a gavage, 250 mg/kg of aqueous and ethanol extracts respectively for 12weeks. Groups 4 and 5 were diabetic rats and were treated with the respective dose of aqueous and ethanol extracts for the same period. A significant (P˂0.05) progressive decrease in blood glucose concentrations of both normal and diabetic rats treated with the extracts were observed from the 2nd to 12th weeks when compared with the respective controls. No significant (P˃0.05) effects were observed in the basal values of both normal and diabetic rats. Administration of both extracts of SH to diabetic rats significantly (P˂0.05) lowered the concentrations of Total cholesterol, TG, and LDL, whereas it increases the concentration of HDL when compared with diabetic control. The concentrations of total cholesterol and LDL in normal rats treated with SH were also reduced when compared with normal control whereas SH had no significant (P˃0.05) effect on HDL. However, TG level of normal control was significantly (P˂0.05) lower than normal rats treated with both extracts. A progressive increase in weight of normal and diabetic rats treated with the extracts was observed on the 2nd – 12th weeks of administration, whereas diabetic control showed a progressive decrease in weight. The findings from this study indicated that SH has hypoglycemic and anti-lipidemic properties as well as anti-diabetic potentials. It also showed that ethanol extract had greater glucose lowering effect. Hence, SH may be considered as a potent anti-diabetic plant and could be used as alternative drug for the management of diabetes mellitus.

Keywords: concentration, ethanol extract, hypoglycemic, total cholesterol

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Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava

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Nanosized environmentally responsive materials are of special interest for various applications, including targeted drug to a considerable potential for treatment of many human diseases. The important technological advantages of nanoparticles (NPs) usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic (water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. As the next step of this research an evaluation of biocompatibility and bioavailability of the synthesized NPs has been performed, using two stable human cell culture lines – HeLa and A549. This part of study is still in progress now.

Keywords: amino acids, biodegradable polymers, nanoparticles (NPs), non-toxic building blocks

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Authors: Pavel Porubiak, Lukas Kudlacek

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Introduction Transplant tourism is a controversial method of obtaining an organ, and that goes all the more for a country such as China, where sources of evidence point out to the possibility of organs being harvested illegally. This research aimed at listing the individual countries these tourists come from, or which medical companies sell transplant related products in there, with China being used as an example. Materials and methods The methodology of scoping study was used for both parts of the research. The countries from which transplant tourists come to China were identified by a search through existing medical studies in the NCBI PubMed database, listed under the keyword ‘transplantation in China’. The search was not limited by any other criteria, but only the studies available for free – directly on PubMed or a linked source – were used. Other research studies on this topic were considered as well. The companies were identified through multiple methods. The first was an online search focused on medical companies and their products. The Bloomberg Service, used by stock brokers worldwide, was then used to identify the revenue of these companies in individual countries – if data were available – as well as their business presence in China. A search through the U.S. Securities and Exchange Commission was done in the same way. Also a search on the Chinese internet was done, and to obtain more results, a second online search was done as well. The results and discussion The extensive search has identified 14 countries with transplant tourists to China. The search for a similar studies or reports resulted in finding additional six countries. The companies identified by our research also amounted to 20. Eight of them are sourcing China with organ preservation products – of which one is just trying to enter the Chinese market, six with immunosuppressive drugs, four with transplant diagnostics, one with medical robots which Chinese doctors use for transplantation as well, and another one trying to enter the Chinese market with a consumable-type product also related to transplantation. The conclusion The question of the ethicality of transplant tourism may be very pressing, since as the research shows, just the sheer amount of participating countries, sourcing transplant tourists to another one, amounts to 20. The identified companies are facing risks due to the nature of transplantation business in China, as officially executed prisoners are used as sources, and widely cited pieces of evidence point out to illegal organ harvesting. Similar risks and ethical questions are also relevant to the countries sourcing the transplant tourists to China.

Keywords: China, illegal organ harvesting, transplant tourism, organ harvesting technology

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Authors: Jerzy Slowik, Elzbieta Grochowska-Niedworok

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The analysis of the market needs and trends in both treatment and prophylaxis shows the growing need to implement comprehensive solutions that would enable safe contact of the beneficiaries with the therapeutic and diagnostic support group. Based on the evaluation of the medical and sports industry services market, projects co-financed by the EFRR in the form of comprehensive care systems using IT tools for patients under treatment in the field of obesity and metabolism using the system were implemented under the Regional Operational Program of the Silesian Voivodeship for 2014-2020. SFAO 1.0 (Support for the Fight Against Obesity) number of the WND-RPSL project. 01.02.00-24-06EA / 16) as well as for competitors in qualified sports SK system (qualified sports) project number WND-RPSL. 01.02.00-24-0630 / 17-002. The service provided in accordance with SFAO 1.0 has shown a wide range of therapy possibilities - from monitoring the body's reactions during sports activities of healthy people to remote care for sick patients. As a result of the introduction of an innovative service, it was possible to increase the effectiveness of the therapy, which was manifested in the reduction of the starting doses of drugs by 10%, improvement of the efficiency of the respiratory and blood circulation system, and a 10% increase in bone density. Innovation in the provision of medical services in the field of qualified sports SK was a response to the needs of the athletes and their parents, coaches, physiotherapists, dieticians, and doctors who take care of people actively practicing qualified sports. The creation of the platform made it possible to constantly monitor the trainers necessary for both the proper training process and the control over the health of patients. Monitoring the patient's health by a specialized team in the field of various specialties allows for the proper targeting of the treatment and training process due to the increase in the availability of medical counseling. Specialists taking care of the patient can provide additional advice and modify the medical treatment of the patient on an ongoing basis, which is why we are dealing with a holistic approach.

Keywords: innovation of medical services, sport, obesity, innovation

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Authors: Menna Ewida, Dalal Abou El-Ella, Dina Lasheen, Huessin El-Subbagh

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Introduction: Vascular Endothelial Growth Factor receptor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis to create new blood vessels. VEGF family binds to three trans-membrane tyrosine kinase receptors,Dihydrofolate reductase (DHFR) is an enzyme of crucial importance in medicinal chemistry. DHFR catalyzes the reduction 7,8 dihydro-folate to tetrahydrofolate and intimately couples with thymidylate synthase which is a pivotal enzyme that catalysis the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) utilizing N5,N10-methylene tetrahydrofolate as a cofactor which functions as the source of the methyl group. Purpose: Novel substituted Thiazole agents were designed as DHFR and VEGF-TK inhibitors with increased synergistic activity and decreased side effects. Methods: Five series of compounds were designed with a rational that mimic the pharmacophoric features present in the reported active compounds that target DHFR & VEGFR. These molecules were docked against Methotrexate & Sorafenib as controls. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. The in silico molecular docking & ADMET study were also applied to the non-classical antifolates for comparison. The interaction energy comparable to that of MTX for DHFRI and Sorafenib for VEGF-TKI activity were recorded. Results: Compound 5 exhibited the highest interaction energy when docked against Sorafenib, While Compound 9 showed the highest interaction energy when docked against MTX with the perfect binding mode. Comparable results were also obtained for the ADMET study. Most of the compounds showed absorption within (95-99) zone which varies according to the type of substituents. Conclusions: The Substituted Thiazole Analogues could be a suitable template for antitumor drugs that possess enhanced bioavailability and act as DHFR and VEGF-TK inhibitors.

Keywords: anti-tumor agents, DHFR, drug design, molecular modeling, VEGFR-TKIs

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Authors: Grzegorz Swiderski, Agata Jablonska-Trypuc, Natalia Popow, Renata Swislocka, Wlodzimierz Lewandowski

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Doxorubicin belongs to the group of anthracycline antitumor antibiotics. Because of the wide spectrum of actions, it is one of the most widely used anthracycline antibiotics, including the treatment of breast, ovary, bladder, lung cancers as well as neuroblastoma, lymphoma, leukemia and myeloid leukemia. Antitumor activity of doxorubicin is based on the same mechanisms as for most anthracyclines. Like the metal ions affect the nucleic acids on many biological processes, so the environment of the metal chelates of antibiotics can have a significant effect on the pharmacological properties of drugs. Complexation of anthracyclines with metal ions may contribute to the production of less toxic compounds. In the framework of this study, the composition of complexes obtained in aqueous solutions of doxorubicin with metal ions (Cu2+ and Zn2+). Complexation was analyzed by spectrophotometric titration in aqueous solution at pH 7.0. The pH was adjusted with 0.02M Tris-HCl buffer. The composition of the complexes found was Cu: doxorubicin (1: 2) and a Zn: doxorubicin (1: 1). The effect of Dox, Dox-Cu and Dox-Zn was examined in MCF-7 breast cancer cell line, which were obtained from American Type Culture Collection (ATCC). The compounds were added to the cultured cells for a final concentration in the range of 0,01µM to 0,5µM. The number of MCF-7 cells with division into living and dead, was determined by direct counts of cells with the use of trypan blue dye using LUNA Logos Biosystems cell counter. ApoTox-Glo Triplex Assay (Promega, Madison, Wisconsin, USA) was used according to the manufacturer’s instructions to measure the MCF-7 cells’ viability, cytotoxicity and apoptosis. We observed a decrease in cells proliferation in a dose-dependent manner. An increase in cytotoxicity and decrease in viability in the ApoTox Triplex assay was also showed for all tested compounds. Apoptosis, showed as caspase 3/7 activation, was observed only in Dox treatment. In Dox-Zn and Dox-Cu caspase 3/7 activation was not observed. This work was financially supported by National Science Centre, Poland, under the research project number 2014/13/B/NZ7/02 352.

Keywords: anticancer properties, anthracycline antibiotic, doxorubicine, metal complexes

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

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Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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