Search results for: therapeutic radionuclides

Authors: Chick Loveline Ayoh Epse Ndi

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Our cultural stance has deep implications for the psychological and physical well-being of the old. Cameroon is still rooted on the traditional belief that stipulates that; the aged are best catered for in the family setting where the children and grandchildren are supposed to give in return for services invested on them by the former. This is why up till date, there are no “Rest Homes” or “Convalescent hospitals” despite the rising challenges faced by the aged in this context. Beside the special measure set aside to cater for the aged, such as “Rest Homes” for the healthy, “Convalescent hospitals” are created set to cater for the health of the aged in the Western context with other facilities such as geriatric units. The health care practitioners are aware of aging diseases and have trained human resources like Gerontologists to cater for the aged and aging diseases. Meanwhile, in Africa and Cameroon in particular, such infrastructural and human resources are still to be considered in the health care system. It can be assumed that the aged and aging diseases are still to be considered in the health care system in this context. This is why we talk of therapeutic nihilism, where the aged are mixed up with other categories of patients with no special attention given to them. This qualitative study carried out in the Yaounde, the capital city of Cameroon, with their best referent hospitals, reveal that; the aged and aging diseases are still a myth in this context. Data collected in both private and public health institutions show that there is only one public institution in Cameroon that has a geriatric unit with no specialists. Patients who aretreated in this unit are considered as aged with terminal diseases that need palliative care and not intensive care. Cameroon is still lacking in terms of health care to the aged and ageing diseases. Like other patients, the aged are treated with a lot of laxity and no value. There is an emergency to create special health care units for geriatrics and and train gerontologist. Mentally or physically ill aged faced medical rational with psychodynamic treatment considered as waste of time. The aged are less likely to be regarded salvageable when they enter a hospital in serious conditions due to the lack of specialists and geriatric units for them. The implication of this study is to sensitization the stake holders for an urgent need to extend special care units for the aged and aging diseases in this context.

Keywords: challeng, therapy, agtng, diseases cameroon

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Authors: Ahmed El-Fiqi, Hae-Won Kim

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Incorporation of therapeutic elements such as Sr, Cu and Co into bioglass structure and their release as ions is considered as one of the promising approaches to enhance cellular responses, e.g., osteogenesis and angiogenesis. Here, cobalt as angiogenesis promoter has been incorporated (at 0, 1 and 4 mol%) into sol-gel derived calcium silicate mesoporous bioglass nanoparticles. The composition and structure of cobalt-free (CFN) and cobalt-doped (CDN) mesoporous bioglass nanoparticles have been analyzed by X-ray fluorescence (XRF), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier-Transform Infra-red spectroscopy (FT-IR). The physicochemical properties of CFN and CDN have been investigated using high-resolution transmission electron microscopy (HR-TEM), Selected area electron diffraction (SAED), and Energy-dispersive X-ray (EDX). Furthermore, the textural properties, including specific surface area, pore-volume, and pore size, have been analyzed from N²⁻sorption analyses. Surface charges of CFN and CDN were also determined from surface zeta potential measurements. The release of ions, including Co²⁺, Ca²⁺, and SiO₄⁴⁻ has been analyzed using inductively coupled plasma atomic emission spectrometry (ICP-AES). Loading and release of diclofenac as an anti-inflammatory drug model were explored in vitro using Ultraviolet-visible spectroscopy (UV-Vis). XRD results ensured the amorphous state of CFN and CDN whereas, XRF further confirmed that their chemical compositions are very close to the designed compositions. HR-TEM analyses unveiled nanoparticles with spherical morphologies, highly mesoporous textures, and sizes in the range of 90 - 100 nm. Moreover, N²⁻ sorption analyses revealed that the nanoparticles have pores with sizes of 3.2 - 2.6 nm, pore volumes of 0.41 - 0.35 cc/g and highly surface areas in the range of 716 - 830 m²/g. High-resolution XPS analysis of Co 2p core level provided structural information about Co atomic environment and it confirmed the electronic state of Co in the glass matrix. ICP-AES analysis showed the release of therapeutic doses of Co²⁺ ions from 4% CDN up to 100 ppm within 14 days. Finally, diclofenac loading and release have ensured the drug/ion co-delivery capability of 4% CDN.

Keywords: mesoporous bioactive glass, nanoparticles, cobalt ions, release

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Authors: Moustafa Ali Elwan, Ibrahim Salem Abdelrafa, Ashraf Moharm

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed oral and topical drugs worldwide. Moreover, NSAIDs are responsible for most of all adverse drug reactions. For several decades, there are numerous attempts to use the cutaneous layers as a gate into the body for the local delivery of the therapeutic agent. Transdermal drug delivery is a validated technology contributing significantly to global pharmaceutical care. Transdermal Drug Delivery systems can be improved by using therapeutic agents. Moreover, Transdermal Drug Delivery systems can be improved by using chemical enhancers like ultrasound or iontophoresis. Iontophoresis provides a mechanism to enhance the penetration of hydrophilic and charged molecules across the skin. Objective: to compare the drug administration by ‘iontophoresis’ versus the oral rule. Methods: This study was conducted at the Faculty of Physical Therapy, Modern University for technology and information, Cairo, Egypt, on 20 participants (8 female & 12 male) who complained of tennis elbow. Their mean age was (25.45 ± 3.98) years, and all participants were assessed in many aspects: Pain threshold was assessed by algometer. Range of motion was assessed by electro goniometer, and isometric strength was assessed by a portable hand-held dynamometer. Then Participants were randomly assigned into two groups: group A was treated with oral NSAID (diclofenac) while group B was treated via administration of NSAIDs (diclofenac) via an iontophoresis device. All the participants were subjected to blood samples analysis in both pre-administration of the drug and post-administration of the drug for 24 hours (sample/every 6 hours). Results: The results demonstrated that there was a significant improvement in group b, “iontophoresis NSAIDs group,” more than in group B,” oral NSAIDs group,” in all measurements ‘ pain threshold, strength, and range of motion. Also, the iontophoresis method shows higher maximum plasma concentrations (Cmax) and concentration-time curves than the oral method.

Keywords: diclofenac, iontophoresis, NSAIDs, oral, tennis elbow

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Authors: Ahn Christine Myunghee, Sim Wonjin, Cho Kristina, Ahn Mira, Hong Yeju, Kwok Jihae, Lim Sooyeon, Park Hansol

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With a sharp increase in the prevalence rate for mental health issues in Korea, there is a need for specific and effective intervention strategies in counseling and psychotherapy for use with Korean clients. With the cultural emphasis on restraining emotional expression and not disclosing personal and familial problems to outsiders, clients often find it difficult to discuss their emotional issues even to therapists. Exploring a client’s internal psychological processes bypassing this culture-specific mode of therapeutic communication often becomes a challenge in the therapeutic setting. Given this socio-cultural context, the purpose of the current study was to investigate the effectiveness of using dream work to individuals in Korea. The current study conducted one 60-90 minute dream session and analyzed the dream content of 39 Korean young adults to evaluate the effectiveness of the Hill dream model in accessing the intra-psychic materials, determining essential emotional themes, and learning how the individuals interpreted the contents of their dreams. The transcribed data, which included a total of 39 sessions from 39 volunteer university students, were analyzed by the Consensus Qualitative Research (CQR) approach in terms of domains and core ideas. Self-report measures on Dream Salience, Gains from Dream Interpretations and the Session Evaluation Scale were administered before and after each of their dream sessions. The results indicated that dream work appears to be an effective way to understand unconscious motivations, thoughts, and feelings related to a person’s sense of self, and also how these people relate to other people. Current findings need to be replicated with clients referred for counseling and psychotherapy to determine if the dream work is an appropriate and useful intervention in counseling settings. Limitations of the current study and suggestions for future follow-ups are included in the discussion.

Keywords: dream work, dream interpretation, Korean, young adults, CQR

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Authors: Aravind Kumar

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The high terrains of Garhwal (Uttarakhand) Himalaya are the niches of a number of rare and endemic plant species of great therapeutic importance. However, the wild flora of the area is still under a constant threat due to rapid upsurge in human interferences, especially through multifarious tourism growth and peri-urban encroachments. After getting the status of a ‘Special State’ of the country since its inception in the year 2000, this newly borne State led to very rapid infrastructural growth and development. Consequently, its townships started expanding in an unmanaged way grabbing nearby agricultural lands and forest areas into peri-urban landscapes. Simultaneously, a boom in tourism and pilgrimage in the state and the infrastructural facilities raised by the government for tourists/pilgrims are destroying its biodiversity. Field survey revealed 242 plant species of therapeutic significance naturally growing in the area and being utilized by local inhabitants as traditional medicines. On conservation scale, 6 species (2.2%) were identified as critically endangered, 19 species (7.1%) as the endangered ones, 8 species (3.0%) under rare category, 17 species (6.4%) as threatened and 14 species (5.2%) as vulnerable. The Government of India has brought mega-biodiversity hot spots of the state under Biosphere Reserve, National Parks, etc. restricting all kinds of human interferences; however, the two most sacred shrines of Hindus and Sikhs viz. Shri Badrinath and Shri Hemkunt Sahib, and two great touristic attractions viz. Valley of Flowers and Auli-Joshimath Skiing Track oblige the government to maintain equilibrium between entries of visitors vis-à-vis biodiversity conservation in high terrains of Uttarakhand Himalaya.

Keywords: biodiversity conservation, ethno-botany, Garhwal (Uttarakhand) Himalaya, peri-urban encroachment, pilgrimage and tourism

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

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Authors: Sergio Alejandro Cuevas, Catherine Etchebest, Fernando Luis Barroso Da Silva

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The flavivirus genus has several organisms responsible for generating various diseases in humans. Special in Brazil, Zika (ZIKV), Dengue (DENV) and Yellow Fever (YFV) viruses have raised great health concerns due to the high number of cases affecting the area during the last years. Diagnostic is still a difficult issue since the clinical symptoms are highly similar. The understanding of their common structural/dynamical and biomolecular interactions features and differences might suggest alternative strategies towards differential serological diagnostics and therapeutic intervention. Due to their immunogenicity, the primary focus of this study was on the ZIKV, DENV and YFV non-structural proteins 1 (NS1) protein. By means of computational studies, we calculated the main physical chemical properties of this protein from different strains that are directly responsible for the biomolecular interactions and, therefore, can be related to the differential infectivity of the strains. We also mapped the electrostatic differences at both the sequence and structural levels for the strains from Uganda to Brazil that could suggest possible molecular mechanisms for the increase of the virulence of ZIKV. It is interesting to note that despite the small changes in the protein sequence due to the high sequence identity among the studied strains, the electrostatic properties are strongly impacted by the pH which also impact on their biomolecular interactions with partners and, consequently, the molecular viral biology. African and Asian strains are distinguishable. Exploring the interfaces used by NS1 to self-associate in different oligomeric states, and to interact with membranes and the antibody, we could map the strategy used by the ZIKV during its evolutionary process. This indicates possible molecular mechanisms that can explain the different immunological response. By the comparison with the known antibody structure available for the West Nile virus, we demonstrated that the antibody would have difficulties to neutralize the NS1 from the Brazilian strain. The present study also opens up perspectives to computationally design high specificity antibodies.

Keywords: zika, biomolecular interactions, electrostatic interactions, molecular mechanisms

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Authors: Wan-Ting Kuo, Yi-Wen Liu, Hsiao-Sheng Liu

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Annual incidence of bladder cancer increases in the world and occurs frequently in the male. Most common type is transitional cell carcinoma (TCC) which is treated by transurethral resection followed by intravesical administration of agents. In clinical treatment of bladder cancer, chemotherapeutic drugs-induced apoptosis is always used in patients. However, cancers usually develop resistance to chemotherapeutic drugs and often lead to aggressive tumors with worse clinical outcomes. Approximate 70% TCC recurs and 30% recurrent tumors progress to high-grade invasive tumors, indicating that new therapeutic agents are urgently needed to improve the successful rate of overall treatment. Nonapoptotic program cell death may assist to overcome worse clinical outcomes. Autophagy which is one of the nonapoptotic pathways provides another option for bladder cancer patients. Autophagy is reported as a potent anticancer therapy in some cancers. First of all, we established a mouse orthotopic bladder tumor formation model in order to create a similar tumor microenvironment. IVIS system and micro-ultrasound were utilized to noninvasively monitor tumor formation. In addition, we carried out intravesical treatment in our animal model to be consistent with human clinical treatment. In our study, we carried out intravesical instillation of the autophagy inducer in mouse orthotopic bladder tumor to observe tumor formation by noninvasive IVIS system and micro-ultrasound. Our results showed that bladder tumor formation is suppressed by the autophagy inducer, and there are no significant side effects in the physiology of mice. Furthermore, the autophagy inducer upregulated autophagy in bladder tissues of the treated mice was confirmed by Western blot, immunohistochemistry, and immunofluorescence. In conclusion, we reveal that a novel autophagy inducer with low side effects suppresses bladder tumor formation in our mouse orthotopic bladder tumor model, and it provides another therapeutic approach in bladder cancer patients.

Keywords: bladder cancer, transitional cell carcinoma, orthotopic bladder tumor formation model, autophagy

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Authors: Ahmed Assem Abd El Rahim

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BACKGROUND: Low back pain (LBP) is enormously common health problem& most of subjects experience it at some point of their life. Kinesio-taping is one of therapy methods introduced for studied cases with nonspecific low back pain. OBJECTIVES: to look at how Kinesio-taping affects studied cases with non-specific low back pain in terms of discomfort, range of motion, & back muscular strength. SUBJECTS: 40 mechanical LBP patients aged 20-40 years had been assigned haphazardly into two groups, They had been selected from outpatient clinic, KasrAl-AiniHospital, Cairo university. Methods: GroupA: 20 patients received the I-shape KT longitudinally & conventional physiotherapy program. Group B:20 studied cases received application of the KT Horizontally & conventional physiotherapy program. pain had been measured by visual analog scale, Range of motion had been measured by Roland Morris Disability Questionnaire (RMDQ), & strength had been measured by an isokinetic dynamometer before & after therapy. Therapy sessions had been three times weekly for four weeks. RESULTS: Groups (A & B) discovered decrease in pain& disability and rise in their flexion, extension ROM & peak torque of trunk extensor after end of 4 weeks of program. mean values of pain scale after therapy had been 3.7 and 5.04 in groups A & B. mean values of Disability scale after treatment had been 7.87.and 9.35 in groups A & B. mean values of ROM of flexion had been 28.06, and 24.53 in groups A & B. mean values of ROM of extension had been 13.43 & 10.73 in groups A & B. mean values of Peak torque of lumbar extensors were 65.43 and 63.22 in groups A & B. Though, participants who received the I-shape KT longitudinally as well as conventional physiotherapy program (group A), discovered more reduction in pain& disability and more improvement in ROM of flexion, extension, and Peak torque of lumbar extensors value (P<0.001) after therapy program CONCLUSION: Therapeutic longitudinal Kinesio-taping application with conventional physiotherapy will be more valuable than Therapeutic horizontal Kinesio-taping application with conventional physiotherapy when treating nonspecific low back pain studied cases.

Keywords: Kinesio taping, function, low back pain, muscle power

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Authors: Eitan Yefenof

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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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Authors: Caroline S. Dutra, Tatiana C. Squeff

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It is well known that the history between South Korea and Japan influences their international relations; thus, also encompassing their economic relations. In this sense, it is impossible to analyze the latter without understanding the development of the former, which is known for episodes of hostility, like on Japanese colonization, but also had moments of cultural and trade interexchange. Indeed, since 1965, with the establishment of diplomatic relations between both countries, their trade relations have improved, especially after both nations have signed the General Agreement on Tariffs and Trade (GATT). Thereafter, with the establishment of the World Trade Organization (WTO) in 1995, another chapter of their diplomatic and economic relations have been inaugurated. Hence, bearing in mind this history between both nations, this research intends to examine their relations through the analysis of the WTO panels they have engaged in between each other, which are, in chronological order, “DS323: Japan – Import Quotas on Dried Laver and Seasoned Laver”, “DS336: Japan - Countervailing Duties on Dynamic Random Access Memories from Korea”, “DS495: Korea - Import Band, and Testing and Certification Requirements for Radionuclides”, “DS553: Korea - Sunset Review of Anti-Dumping Duties on Stainless Steel Bars” and “DS571: Korea - Measures Affecting Trade in Commercial Vessels”. The objective of this case analysis is to point out what are the areas that are more conflictual between Japan and South Korea in regard to their economic relations so that it is possible to assert on their future (economic) relations and other possible outcomes. And in order to do so, bibliographic and documental research will be made, particularly those involving the WTO and the nations under consideration. Regarding the methods used, it is important to highlight that this is applied research in the field of international economic relations and international law, which follows a hypothetic-deductive model.

Keywords: international economic relations, Japan, South Korea, World Trade Organization

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Authors: Antonio Montes, Antonio Cozar, Clara Pereyra, Diego Valor, Enrique Martinez de la Ossa

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Tissues and organs can be damaged because of traumatism, congenital illnesses, or cancer and the traditional therapeutic alternatives, such as surgery, cannot usually completely repair the damaged tissues. Tissue engineering allows regeneration of the patient's tissues, reducing the problems caused by the traditional methods. Scaffolds, polymeric structures with interconnected porosity, can be promoted the proliferation and adhesion of the patient’s cells in the damaged area. Furthermore, by means of impregnation of the scaffold with beneficial active substances, tissue regeneration can be induced through a drug delivery process. The objective of the work is the fabrication of a PVA scaffold coated with Gallic Acid and polypyrrole through a one-step foaming and impregnation process using the SSI technique (Supercritical Solvent Impregnation). In this technique, supercritical CO₂ penetrates into the polymer chains producing the plasticization of the polymer. In the depressurization step a CO₂ cellular nucleation and growing to take place to an interconnected porous structure of the polymer. The foaming process using supercritical CO₂ as solvent and expansion agent presents advantages compared to the traditional scaffolds’ fabrication methods, such as the polymer’s high solubility in the solvent or the possibility of carrying out the process at a low temperature, avoiding the inactivation of the active substance. In this sense, the supercritical CO₂ avoids the use of organic solvents and reduces the solvent residues in the final product. Moreover, this process does not require long processing time that could cause the stratification of substance inside the scaffold reducing the therapeutic efficiency of the formulation. An experimental design has been carried out to optimize the SSI technique operating conditions, as well as a study of the morphological characteristics of the scaffold for its use in tissue engineerings, such as porosity, conductivity or the release profiles of the active substance. It has been proved that the obtained scaffolds are partially porous, conductors of electricity and are able to release Gallic Acid in the long term.

Keywords: scaffold, foaming, supercritical, PVA, polypyrrole, gallic acid

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Authors: Kenichi Yamahara, Makiko Ohshima, Shunsuke Ohnishi, Hidetoshi Tsuda, Akihiko Taguchi, Toshihiro Soma, Hiroyasu Ogawa, Jun Yoshimatsu, Tomoaki Ikeda

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We have previously reported the therapeutic potential of rat fetal membrane(FM)-derived mesenchymal stem cells (MSCs) using various rat models including hindlimb ischemia, autoimmune myocarditis, glomerulonephritis, renal ischemia-reperfusion injury, and myocardial infarction. In this study, 1) we isolated and characterized MSCs from human amnion and chorion; 2) we examined their differences in the expression profile of growth factors and cytokines; and 3) we investigated the therapeutic potential and difference of these MSCs using murine hindlimb ischemia and acute graft-versus-host disease (GVHD) models. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced T-lymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of GVHD disease. Our results highlight that human amnionand chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.

Keywords: amnion, chorion, fetal membrane, mesenchymal stem cells

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Authors: Rajiv Jash, Himangshusekhar Maji

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Phytomolecules have long been associated with the effective treatment of various disorders since ages. This study focuses on identifying the immunomodulatory pure molecules isolated from plants, which can be studied for their effect in alleviating IgAN. All the phytomolecules mentioned here have inflammation-reducing properties, and IgAN, being an autoimmune disease, can be a good target of these phytomolecules. Various pathological pathways of IgA nephropathy can be targeted with these phytomolecules, and this study is an effort to find out the rationale behind the choice of the molecules based on their ability to target the effector molecules of those pathological pathways.

Keywords: IgAN, fibrosis, inflammation, ESRD, TGFβ

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Authors: Alireza Yavar, Sukiman Sarmani, Kok Siong Khoo

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Trace element analysis of human hair has the potential to disclose retroactive information about an individual’s nutritional status and exposure. The residents of villages in Kandal province of Cambodia, due to dietary habits, lifestyle and ecological conditions, are unprotected from toxic elements particularly arsenic (As). The purpose of this research was to valuation levels of toxic and vital elements in scalp human hair. Scalp hair samples of 12-17 school children from three villages of Anglong Romiot (AR), Svay Romiot (SR) and Kampong Kong (KK) in the Kandal province of Cambodia were evaluated using k0- instrumental neutron activation method (k0-INAA). The samples were irradiated 6 hours in a Malaysian nuclear agency (MNA) research reactor and afterward, an HPGe detector was utilized to obtain gamma peaks of radionuclides in samples. We achieved profiles of 31 elements in human hair in our studied area, namely, As, Au, Br, Ca, Ce, Co, Dy, Eu152m, Hg197, Hg203, Ho, Ir, K, La, Lu, Mn, Na, Pa, Pt195m, Pt197, Sb, Sc46, Sc47, Sm, Sn117m, W181, W187, Yb169, Yb175, Zn and Zn69m. The precision of the method was assessed by evaluating ERM-DB001-human hair as certified reference materials (CRMs), and which experimental result of ERM-DB001 was consistent with certified values. Whereas Arsenic (As) pollution is major contamination in our studied area, correlation between the concentration of As and other elements were determined by Pearson’s correlation test that it may be useful as a database source for toxic and essential elements in the hair of teenage individuals in our studied area

Keywords: scalp human hair, toxic and essential elements, Kandal province of Cambodia, k₀- instrumental neutron activation method

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Authors: Balkibekova Venera Serikpaevna

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Background: Autism Spectrum Disorder (ASD) poses significant challenges in both diagnosis and treatment. Existing therapeutic interventions often target specific symptoms, necessitating the exploration of alternative approaches. This study investigates the RITM (Rhythm Integration Tapping Music) developed by Balkibekova, aiming to create imitation, social engagement and a wide range of emotions through brain development. Methods: A randomized controlled trial was conducted with 100 participants diagnosed with ASD, aged 1 to 4 years. Participants were randomly assigned to either the RITM therapy group or a control group receiving standard care. The RITM therapy, rooted in tapping rhythm to music such as: marche on the drums, waltz on bells, lullaby on musical triangle, dancing on tambourine, polka on wooden spoons. Therapy sessions were conducted over a 3 year period, with assessments at baseline, midpoint, and post-intervention. Results: Preliminary analyses reveal promising outcomes in the RITM therapy group. Participants demonstrated significant improvements in social interactions, speech understanding, birth of speech, and adaptive behaviors compared to the control group. Careful examination of subgroup analyses provides insights into the differential effectiveness of the RITM approach across various ASD profiles. Conclusions: The findings suggest that RITM therapy, as developed by Balkibekova, holds promise as intervention for ASD. The integrative nature of the approach, addressing multiple domains simultaneously, may contribute to its efficacy. Further research is warranted to validate these preliminary results and explore the long-term impact of RITM therapy on individuals with ASD. This abstract presents a snapshot of the research, emphasizing the significance, methodology, key findings, and implications of the RITM therapy method for consideration in an autism conference.

Keywords: RITM therapy, tapping rhythm, autism, mirror neurons, bright emotions, social interactions, communications

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Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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Authors: El-Said. I. Shabana, Mohammad S. Tayeb, Maher M. T. Qutub, Abdulraheem A. Kinsara

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Usually, phosphate deposits contain ²³⁸U and ²³²Th in addition to their decay products. Due to their different pathways in the environment, the ²³⁸U/²³²Th activity concentration ratio usually found to be greater than unity in phosphate sediments. The presence of these radionuclides creates a potential need to control exposure of workers in the mining and processing activities of the phosphate minerals in accordance with IAEA safety standards. The greatest dose to workers comes from exposure to radon, especially ²²²Rn from the uranium series, and has to be controlled. In this regard, radon (²²²Rn) was measured in the atmosphere (indoor and outdoor) of Al-Jalamid phosphate-mines working area using a portable radon-measurement instrument RAD7, in a purpose of radiation protection. Radon was measured in 61 sites inside the open phosphate mines, the phosphate upgrading facility (offices and rooms of the workers, and in some open-air sites) and in the dwellings of the workers residence-village that lies at about 3 km from the mines working area. The obtained results indicated that the average indoor radon concentration was about 48.4 Bq/m³. Inside the upgrading facility, the average outdoor concentrations were 10.8 and 9.7 Bq/m³ in the concentrate piles and crushing areas, respectively. It was 12.3 Bq/m³ in the atmosphere of the open mines. These values are comparable with the global average values. Based on the average values, the annual effective dose due to radon inhalation was calculated and risk estimates have been done. The average annual effective dose to workers due to the radon inhalation was estimated by 1.32 mSv. The potential excess risk of lung cancer mortality that could be attributed to radon, when considering the lifetime exposure, was estimated by 53.0x10^-4. The results have been discussed in detail.

Keywords: dosimetry, environmental monitoring, phosphate deposits, radiation protection, radon

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Authors: Shideh Mohseni Movahed, Mansoureh Safari

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Intelligent drug delivery systems (IDDS) are innovative technological innovations and clinical way to advance current treatments. These systems differ in technique of therapeutic administration, intricacy, materials and patient compliance to address numerous clinical conditions that require different pharmacological therapies. IDDS capable of releasing an active molecule at the proper site and at a amount that adjusts in response to the progression of the disease or to certain functions/biorhythms of the organism is particularly appealing. In this paper, we describe the most recent advances in the development of intelligent drug delivery systems.

Keywords: drug delivery systems, IDDS, medicine, health

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Authors: M. I. A. Adziz, J. Sharib Sarip, M. T. Ishak, D. N. A. Tugi

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Radiation exposure to humans and the environment is caused by natural radioactive material sources. Given that exposure to people and communities can occur through several pathways, it is necessary to pay attention to the increase in naturally radioactive material, particularly in the soil. Continuous research and monitoring on the distribution and determination of these natural radionuclides' activity as a guide and reference are beneficial, especially in an accidental exposure. Surface soil/sediment samples from several locations identified around the Sembrong catchment area were taken for the study. After 30 days of secular equilibrium with their daughters, the activity concentrations of the naturally occurring radioactive material (NORM) members, i.e. ²²⁶Ra, ²²⁸Ra, ²³⁸U, ²³²Th, and ⁴⁰K, were measured using high purity germanium (HPGe) gamma spectrometer. The results obtained showed that the radioactivity concentration of ²³⁸U ranged between 17.13 - 30.13 Bq/kg, ²³²Th ranged between 22.90 - 40.05 Bq/kg, ²²⁶Ra ranged between 19.19 - 32.10 Bq/kg, ²²⁸Ra ranged between 21.08 - 39.11 Bq/kg and ⁴⁰K ranged between 9.22 - 51.07 Bq/kg with average values of 20.98 Bq/kg, 27.39 Bq/kg, 23.55 Bq/kg, 26.93 Bq/kg and 23.55 Bq/kg respectively. The values obtained from this study were low or equivalent to previously reported in previous studies. It was also found that the mean/mean values obtained for the four parameters of the Radiation Hazard Index, namely radium equivalent activity (Raeq), external dose rate (D), annual effective dose and external hazard index (Hₑₓ), were 65.40 Bq/kg, 29.33 nGy/h, 19.18 ¹⁰⁻⁶Sv and 0.19 respectively. These obtained values are low compared to the world average values and the values of globally applied standards. Comparison with previous studies (dry season) also found that the values for all four parameters were low and equivalent. This indicates the level of radiation hazard in the area around the study is safe for the public.

Keywords: catchment area, gamma spectrometry, naturally occurring radioactive material (NORM), soil

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Authors: Amos Sunday Onikanni, Bashir Lawal, Babatunji Emmanuel Oyinloye, Gomaa Mostafa-Hedeab, Mohammed Alorabi, Simona Cavalu, Augustine O. Olusola, Chih-Hao Wang, Gaber El-Saber Batiha

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The increasing global burden of diabetes mellitus has called for the search for a therapeutic alternative that offers better activities and safety than conventional chemotherapy. Herein, we evaluated the neuroprotective and antioxidant properties of different fractions (ethyl acetate, N-butanol and residual aqueous) of Clompanus pubescens leaves in streptozotocin (STZ)-induced diabetic rats. Our results revealed a significant elevation in the levels of blood glucose, pro-inflammatory cytokines, lipid peroxidation, neuronal activities of acetylcholinesterase, butyrylcholinesterase, nitric oxide, epinephrine, norepinephrine, and Na+/K+-ATPase in diabetic non treated rats. In addition, decreased levels of enzymatic and non-enzymatic antioxidants were observed. Treatment with different fractions of C. pubescens leaves resulted in a significant reversal of the biochemical alteration and improved the neurocognitive deficit in STZ-induced diabetic rats. However, the ethyl-acetate fraction demonstrated higher activities than the other fractions and was characterized for its phytoconstituents, revealing the presence of Gallic acid (713.00 ppm), catechin (0.91 ppm), ferulic acid (0.98 ppm), rutin (59.82 ppm), quercetin (3.22 ppm) and kaempferol (4.07 ppm). Our molecular docking analysis revealed that these compounds exhibited different binding affinities and potentials for targeting BChE/AChE/ IL-1 β/Na+-K+-ATPase. However, only Kampferol and ferulic exhibited good drug-like, ADMET, and permeability properties suitable for use as a neuronal drug target agent. Hence, the ethyl-acetate fraction of C. pubescent leaves could be considered a source of promising bioactive metabolite for the treatment and management of cognitive impairments related to type II diabetes mellitus.

Keywords: diabetes mellitus, neuroprotective, antioxidant, pro-inflammatory cytokines

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Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

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Authors: Hami Ashraf, Mohammad Heydarnejad

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Introduction: The landscape of cancer treatment has been revolutionized by immunotherapy, offering novel therapeutic avenues for diverse cancer types. Animal models play a pivotal role in the development and elucidation of these therapeutic modalities. Nevertheless, the manifestation of Graft-versus-Host Disease (GVHD) in such models poses significant challenges, muddling the interpretation of experimental data within the ambit of cancer immunotherapy. This study is dedicated to scrutinizing the role of GVHD as a confounding factor in animal models used for cancer immunotherapy, alongside proposing viable strategies to mitigate this complication. Method: Employing a systematic review framework, this study undertakes a comprehensive literature survey including academic journals in PubMed, Embase, and Web of Science databases and conference proceedings to collate pertinent research that delves into the impact of GVHD on animal models in cancer immunotherapy. The acquired studies undergo rigorous analysis and synthesis, aiming to assess the influence of GVHD on experimental results while identifying strategies to alleviate its confounding effects. Results: Findings indicate that GVHD incidence significantly skews the reliability and applicability of experimental outcomes, occasionally leading to erroneous interpretations. The literature surveyed also sheds light on various methodologies under exploration to counteract the GVHD dilemma, thereby bolstering the experimental integrity in this domain. Conclusion: GVHD's presence critically affects both the interpretation and validity of experimental findings, underscoring the imperative for strategies to curtail its confounding impacts. Current research endeavors are oriented towards devising solutions to this issue, aiming to augment the dependability and pertinence of experimental results. It is incumbent upon researchers to diligently consider and adjust for GVHD's effects, thereby enhancing the translational potential of animal model findings to clinical applications and propelling progress in the arena of cancer immunotherapy.

Keywords: graft-versus-host disease, cancer immunotherapy, animal models, preclinical model

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Authors: B. Sadepovich Maikanov, Z. Shabanbayevich Adilbekov, R. Husainovna Mustafina, L. Tyulegenovna Auteleyeva

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This study involves detailed information about contaminants of honey in the Republic of Kazakhstan. The requirements of the technical regulation ‘Requirements to safety of honey and bee products’ and GOST 19792-2001 were taken into account in this research. Contamination of honey by antibiotics wqs determined by the IEA (immune-enzyme analysis), Ridder analyzer and Tecna produced test systems. Voltammetry (TaLab device) was used to define contamination by salts of heavy metals and gamma-beta spectrometry, ‘Progress BG’ system, with preliminary ashing of the sample of honey was used to define radioactive contamination. This article pointed out that residues of chloramphenicol were detected in 24% of investigated products, in 22% of them –streptomycin, in 7.3% - sulfanilamide, in 2.4% - tylosin, and in 12% - combined contamination was noted. Geographically, the greatest degree of contamination of honey with antibiotics occurs in the Northern Kazakhstan – 54.4%, and Southern Kazakhstan - 50%, and the lowest in Central and Eastern Kazakhstan with 30% and 25%, respectively. Generally, pollution by heavy metals is within acceptable limits, but the contamination from lead is highest in the Akmola region. The level of radioactive cesium and strontium is also within acceptable concentrations. The highest radioactivity in terms of cesium was observed in the East Kazakhstan region - 49.00±10 Bq/kg, in Akmola, North Kazakhstan and Almaty - 12.00±5, 11.05±3 and 19.0±8 Bq/kg, respectively, while the norm is 100 Bq/kg. In terms of strontium, the radioactivity in the East Kazakhstan region is 25.03±15 Bq/kg, while in Akmola, North Kazakhstan and Almaty regions it is 12.00±3, 10.2±4 and 1.0±2 Bq/kg, respectively, with the norm of 80 Bq/kg. This accumulation is mainly associated with the environmental degradation, feeding and treating of bees. Moreover, in the process of collecting nectar, external substances can penetrate honey. Overall, this research determines factors and reasons of honey contamination.

Keywords: antibiotics, contamination of honey, honey, radionuclides

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Authors: Navneet Sharma, Himanshu Ojha, Dharam Pal Pathak, Rakesh Kumar Sharma

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Radio-nuclides decontamination is an important task because any extra second of deposition leads to deleterious health effects. We had developed and characterise nanoemulsion of p-tertbutylcalix[4]arens using phase inversion temperature (PIT) method and evaluate its decontamination efficacy (DE). The solubility of the drug was determined in various oils and surfactants. Nanoemulsion developed with an HLB value of 11 and different ratios of the surfactants 10% (7:3, w/w), oil (20%, w/w), and double distilled water (70%) were selected. Formulation was characterised by multi-photon spectroscopy and parameters like viscosity, droplet size distribution, zeta potential and stability were optimised. In vitro and Ex vivo decontamination efficacy (DE) was evaluated against Technetium-99m, Iodine-131, and Thallium-201 as radio-contaminants applied over skin of Sprague-Dawley rat and human tissue equivalent model. Contaminants were removed using formulation soaked in cotton swabs at different time intervals and whole body imaging and static counts were recorded using SPECT gamma camera before and after decontamination attempt. Data were analysed using one-way analysis of variance (ANOVA) and was found to be significant (p <0.05). DE of the nanoemulsion loaded with p-tertbutylcalix[4]arens was compared with placebo and recorded to be 88±5%, 90±3% and 89±3% for 99mTc, 131I and 201Tl respectively. Ex-vivo complexation study of p-tertbutylcalix[4]arene nanoemulsion with surrogate nuclides of radioactive thallium and Iodine, were performed on rat skin mounted on Franz diffusion cell using high-resolution sector field inductively coupled plasma mass spectroscopy (HR-SF-ICPMS). More than 90% complexation of the formulation with these nuclides was observed. Results demonstrate that the prepared nanoemulsion formulation was found efficacious for the decontamination of radionuclides from a large contaminated population.

Keywords: p-tertbutylcalix[4]arens, skin decontamination, radiological emergencies, nanoemulsion, iodine-131, thallium-201

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Authors: Satoshi Nishimura

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Although much information has been garnered from the genomes of humans and mice, it remains difficult to extend that information to explain physiological and pathological phenomena. This is because the processes underlying life are by nature stochastic and fluctuate with time. Thus, we developed novel "in vivo molecular imaging" method based on single and two-photon microscopy. We visualized and analyzed many life phenomena, including common adult diseases. We integrated the knowledge obtained, and established new models that will serve as the basis for new minimally invasive therapeutic approaches.

Keywords: two photon microscope, intravital visualization, thrombus, artery

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Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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Authors: Hang T. T. Tran, Ha T. Le, Hanh T. P. Tran, Hung V. Cao, Giang T. H. Nguyen, Dien M. Tran, Tobias Alfvén, Linus Olson

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Background: Hypoxic Ischemic Encephalopathy is one of the major causes of neonatal death and those who survive with severe encephalopathy are more likely to develop adverse long-term outcomes such as neurocognitive impairment and cerebral palsy, which is a huge burden, especially in low-middle income countries. It is important to have a long-term follow-up for early detection and promote early intervention for these groups of high-risk infants. Aim: To determine the neurological outcome of cooling infants at 18 months and identify an optimized neurological examination scale for Hypoxic Ischemic Encephalopathy infants in Vietnam. Method: Descriptive study of neurodevelopmental outcomes at 18 months of HIE infants who underwent therapeutic hypothermia treatment in Vietnam. All survived cooling infants were assessed at discharge and at 6, 12, and 18 months by a pediatric physical therapist and a neurologist using two assessment tools: Ages and Stages Questionnaires and the Hammersmith Infant Neurological Examination scale to detect impairments and promote early intervention for those who require it. Results: During a 3-year period, a total of 130 neonates with moderate to severe HIE underwent therapeutic hypothermia treatment using Phase change material mattress (65% moderate, 35% severe – Sarnat). 43 (33%) died during hospitalization and infancy; among survivors, 69 (79%) completed 3 follow-ups at 18 months. At 18 months, 25 had cerebral palsy, 11 had mild delayed neurodevelopment. At each time-point, infants with a normal/mildly delayed neurodevelopment had significantly higher Ages and Stages Questionnaires and Hammersmith Infant Neurological Examination scores (p<0.05) than those with cerebral palsy. Conclusion: The study showed that the Ages and Stages Questionnaires and Hammersmith Infant Neurological Examination is a helpful tool in the process of early diagnosis of infants at low and high neurological risk and identifying those infants needing specific rehabilitation programme.

Keywords: encephalopathy, phase-change-material, neurodevelopment, cerebral palsy

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Authors: Avani Jain, Hasmukh Jain, S. Shelley, M. Indirani, Shilpa Kalal, Jayakanth Amalachandran

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Aim of the Study: To assess the effect of orally administered Itopride on gall bladder ejection fraction by fatty meal cholescintigraphy in patients with diabetes. Materials and Methods: Thirty patients (20 males, 10 females, mean age 46+10 yrs) with history of diabetes mellitus (mean duration 4.8+4.1 yrs, fasting blood glucose level 130+35 mg/dl and 2-hours post-prandial blood glucose level 196+76 mg/dl) and found to have gall bladder dysfunction on fatty-meal stimulated cholescintigraphy were selected for this study. These patients underwent a repeat cholescintigraphy similar to baseline study, with 50 mg of Itopride orally along with fatty meal. Pre- and post-Itopride GBEF were then compared to assess the effect of Itopride on gall bladder contraction. Results: Out of these 30 patients, 2 had dyskinetic, 4 had akinetic, 22 had moderately hypokinetic and the remaining 2 had hypokinetic gall bladder function in the baseline study with > 60% GBEF being taken as the normal value. Mean percentage of GBEF in the baseline study was 32%+13% and the mean percentage of GBEF in the post-Itopride study was 57%+17% with change in mean percentage of GBEF being 24%+21%. GBEF of the “baseline study” was significantly lower as compared to GBEF in the “post-Itopride study” (p < 0.05). Conclusion: Diabetic patients with biliary-type pain often tend to have impaired gallbladder function. Cholescintigraphy with fatty meal-stimulation is a simple, cheap and useful investigation for assessment of gallbladder dysfunction in these patients, before any structural changes occur within the lumen or wall of the gall bladder. Improvement in gallbladder ejection fraction after oral administration of a single dose of Itopride, a newer prokinetic drug with fewer side effects, as assessed by cholescintigraphy, provides enough evidence of future therapeutic response. Administration of Itopride, in therapeutic dosage, therefore may be expected to cause significant improvement in gallbladder ejection fraction and hence prolong stone formation within the gall bladder and also prevent the associated long term complications. Hence, based on scintigraphic evidence, Itopride may be recommended, by clinicians, for management of symptomatic diabetic patients having gallbladder dysfunction.

Keywords: itopride, gall bladder ejection fraction, fatty meal, cholescintigraphy, diabetes

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Authors: Vijaya Madhuri Devraj, Swarnalatha Guditi, Kiran Kumar Bokara, Gangadhar Taduri

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Cell-based strategies may open therapeutic approaches that promote tolerance through manipulation of macrophages to increase long-term transplant survival rates and minimize side effects of the current immune suppressive regimens. The aim of the present study was, therefore, to test and compare the therapeutic potential of MSC and Tregs on macrophage polarization to develop an alternate cell-based treatment option in kidney transplantation. In the current protocol, macrophages from kidney transplant recipients with graft dysfunction were co-cultured with MSCs and Treg cells with and without cell-cell contact on transwell plates, further to quantitatively assess macrophage polarization in response to MSC and Treg treatment over time, M1 and M2 cell surface markers were used. Additionally, multiple soluble analytes were analyzed in cell supernatant by using bead-based immunoassays. Furthermore, to confirm our findings, gene expression analysis was done. MSCs induced the formation of M2 macrophages more than Tregs when macrophages M0 were cultured in transwell without cell contact. From this, we deduced the mechanism that soluble factors present in the MSCs condition media are involved in skewing of macrophages towards type 2 macrophages; similarly, in co-culture with cell-cell contact, MSCs resulted in more M2 type macrophages than Tregs. And an important finding of this study is the combination of both MSC-Treg showed significantly effective and consistent results in both with and without cell contact setups. Hence, it is suggestive to prefer MSCs over Tregs for secretome-based therapy and a combination of both for either therapy for effective transplantation outcomes. Our findings underline a key role of Tregs and MSCs in promoting macrophage polarization towards anti-inflammatory type. The study has great importance in prolongation of allograft and patient survival without any rejection by cell-based therapy, which induce self-tolerance and controlling infection.

Keywords: graft rejection, graft tolerance, macrophage polarization, mesenchymal stem cells, regulatory T cells, transplant immunology

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