Search results for: therapeutic healing
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1845

Search results for: therapeutic healing

1305 Autophagy Suppresses Bladder Tumor Formation in a Mouse Orthotopic Bladder Tumor Formation Model

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

Abstract:

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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1304 Effects of Kinesio Taping on Pain and Functions of Chronic Nonspecific Low Back Pain Patients

Authors: Ahmed Assem Abd El Rahim

Abstract:

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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1303 The Molecular Rationale for Steroid Based Therapy of Leukemia: Diagnostic and Therapeutic Implications

Authors: Eitan Yefenof

Abstract:

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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1302 Development of PVA/polypyrrole Scaffolds by Supercritical CO₂ for Its Application in Biomedicine

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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1301 Angiogenic, Cytoprotective, and Immunosuppressive Properties of Human Amnion and Chorion-Derived Mesenchymal Stem Cells

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

Abstract:

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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1300 Phytomolecules Intervening Inflammation in IgA Nephropathy: A Possible Therapeutic Approach

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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1299 In vitro and invivo Antioxidant Studies of Grewia crenata Leaves Extract in Albino Rats

Authors: A. N.Ukwuani, A. K. Abdulfatah

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G. crenata is used locally for the treatment of fractured bones, wound healing and inflammatory conditions. In vitro and in vivo antioxidant activity of hydromethanolic extracts of the leaves of G. crenata were assessed. The phytochemical analysis shows the presence of phenols, flavonoids, saponins, cardiac glycosides and tannins. An in vitro quantitative analysis of phenols, flavonoids and tannins respectively were (164±1.20, 199±0.88 and 88.67±0.88 mg/100g FW). In vivo studies of hydromethanolic extract demonstrated a dose dependent increase in hepatic superoxide dismutase (1.14±0.14, 2.13±0.11, 2.55±0.11 U/mg Protein) with improvement in hepatic glutathione (6.98±0.42, 8.91±0.37, 11.07±0.46 µM/mg Protein) and Catalase (4.47±0.05, 6.24±0.02, 7.17±0.04 U/mg Protein) and Total protein (6.18±0.08, 6.69±0.18, 7.27±0.16 mg/ml) respectively at 100-300mg/kg body weight Grewia crenata leaves when compared to the control and standard drug. It can be concluded from the present findings of that G. crenata leaves possess antioxidant potential.

Keywords: Grewia crenata, antioxidant, hydromethanolic extract, in vivo, in vitro

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1298 Prominence of Biopsychosocial Formulation in Health Care Delivery for Aging Population: Empowering Caregiving through Natural Socio-Environmental Approaches

Authors: Kristine Demilou D. Santiago

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An access to a high-quality health care system is what sets apart industrialized nations, such as the United States from other developing countries, which in this case is specifically pertaining to their older population. But what was the underrated factor in the sphere of quality healthcare rendered to elderly people in the Western context? Will this salient factor could push conviction to prorogue the existing gaps between self-denial patient-client and cheek by jowl medications? Are the natural socio-environmental approaches of caregiving the protracted remedy to healthcare disparities for aging population considering their day to day living? The conceptual framework of this model is primarily associated with addressing health and illness of human beings considering the biological, psychological and socio-environmental factors around them. The relevance of biopsychosocial formulation advancing each of the characteristics in the Biopsychosocial (BPS) model in a balance contemplation is the tumult of this study in an attempt to respond to prevailing disparities in caregiving services for old-aged patients on a day to day living. Caregiving services have been the medium path connecting between the patient and its prescribed medications. Moreover, caregivers serve as positive reinforcers in a patient’s environment. Therefore, caregivers play an important role in healthcare delivery to patients. They are considered significant people whom their acts will give an impact to a patient’s view in life. This research study intends to present the supreme importance of biopsychosocial assessment to old-aged patients with mental health illness and conditions. Biopsychosocial assessment will secure the quality of full medication to an old-aged adult suffering from a mental illness. This is because it offers a recognizably wholesome approach to medical healing of old-aged adult patients. The principle of biopsychosocial supersedes the biomedicine being offered to old-aged adults having mental illness, but it does not take away the high relevance of scientific biomedicine in healing patients. The framework presented an overlapping participation of each of its factors in its BPS model that affects in general a person’s health. The correlation between the biological (physiological), psychological (mental) and social (environment) in a person’s health condition requires equal attention according to BPS, and it always coexist with each other. Indisputably said, bio-medicine has been and is being in its unceasing endeavor to provide scientifically proven health care medications for every individual seeking medical treatments. As we grow older and eventually reach the other side of the median population, not only our physiological aspects change, our psychological and socio-environmental changes happen too. Caregiving is a salient responsibility taking place on these inevitable changes.

Keywords: biopsychosocial formulation, caregiving through natural approaches, US health care, BPS in caregiving, caregiving for aging population

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1297 Responsive Integrative Therapeutic Method: Paradigm for Addressing Core Deficits in Autism by Balkibekova

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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1296 Harnessing Nature's Fury: Hyptis Suaveolens Loaded Bioactive Liposome for Photothermal Therapy of Lung Cancer

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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1295 Intelligent Drug Delivery Systems

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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1294 Therapeutic Efficacy of Clompanus Pubescens Leaves Fractions via Downregulation of Neuronal Cholinesterases/NA⁺-K⁺ ATPase/IL-1 β and Improving the Neurocognitive and Antioxidants Status of Streptozotocin-Induced Diabetic Rats

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

Abstract:

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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1293 Targeting Peptide Based Therapeutics: Integrated Computational and Experimental Studies of Autophagic Regulation in Host-Parasite Interaction

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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1292 Design and Construction of a Home-Based, Patient-Led, Therapeutic, Post-Stroke Recovery System Using Iterative Learning Control

Authors: Marco Frieslaar, Bing Chu, Eric Rogers

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Stroke is a devastating illness that is the second biggest cause of death in the world (after heart disease). Where it does not kill, it leaves survivors with debilitating sensory and physical impairments that not only seriously harm their quality of life, but also cause a high incidence of severe depression. It is widely accepted that early intervention is essential for recovery, but current rehabilitation techniques largely favor hospital-based therapies which have restricted access, expensive and specialist equipment and tend to side-step the emotional challenges. In addition, there is insufficient funding available to provide the long-term assistance that is required. As a consequence, recovery rates are poor. The relatively unexplored solution is to develop therapies that can be harnessed in the home and are formulated from technologies that already exist in everyday life. This would empower individuals to take control of their own improvement and provide choice in terms of when and where they feel best able to undertake their own healing. This research seeks to identify how effective post-stroke, rehabilitation therapy can be applied to upper limb mobility, within the physical context of a home rather than a hospital. This is being achieved through the design and construction of an automation scheme, based on iterative learning control and the Riener muscle model, that has the ability to adapt to the user and react to their level of fatigue and provide tangible physical recovery. It utilizes a SMART Phone and laptop to construct an iterative learning control (ILC) system, that monitors upper arm movement in three dimensions, as a series of exercises are undertaken. The equipment generates functional electrical stimulation to assist in muscle activation and thus improve directional accuracy. In addition, it monitors speed, accuracy, areas of motion weakness and similar parameters to create a performance index that can be compared over time and extrapolated to establish an independent and objective assessment scheme, plus an approximate estimation of predicted final outcome. To further extend its assessment capabilities, nerve conduction velocity readings are taken by the software, between the shoulder and hand muscles. This is utilized to measure the speed of response of neuron signal transfer along the arm and over time, an online indication of regeneration levels can be obtained. This will prove whether or not sufficient training intensity is being achieved even before perceivable movement dexterity is observed. The device also provides the option to connect to other users, via the internet, so that the patient can avoid feelings of isolation and can undertake movement exercises together with others in a similar position. This should create benefits not only for the encouragement of rehabilitation participation, but also an emotional support network potential. It is intended that this approach will extend the availability of stroke recovery options, enable ease of access at a low cost, reduce susceptibility to depression and through these endeavors, enhance the overall recovery success rate.

Keywords: home-based therapy, iterative learning control, Riener muscle model, SMART phone, stroke rehabilitation

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1291 The Confounding Role of Graft-versus-Host Disease in Animal Models of Cancer Immunotherapy: A Systematic Review

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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1290 Numerical Modelling of Effective Diffusivity in Bone Tissue Engineering

Authors: Ayesha Sohail, Khadija Maqbool, Anila Asif, Haroon Ahmad

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The field of tissue engineering is an active area of research. Bone tissue engineering helps to resolve the clinical problems of critical size and non-healing defects by the creation of man-made bone tissue. We will design and validate an efficient numerical model, which will simulate the effective diffusivity in bone tissue engineering. Our numerical model will be based on the finite element analysis of the diffusion-reaction equations. It will have the ability to optimize the diffusivity, even at multi-scale, with the variation of time. It will also have a special feature, with which we will not only be able to predict the oxygen, glucose and cell density dynamics, more accurately, but will also sort the issues arising due to anisotropy. We will fix these problems with the help of modifying the governing equations, by selecting appropriate spatio-temporal finite element schemes, by adaptive grid refinement strategy and by transient analysis.

Keywords: scaffolds, porosity, diffusion, transient analysis

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1289 Cell-Cell Interactions in Diseased Conditions Revealed by Three Dimensional and Intravital Two Photon Microscope: From Visualization to Quantification

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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1288 POSS as Modifiers and Additives for Elastomer Composites

Authors: Anna Strąkowska, Marian Zaborski

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The studies were focused on POSS application with methylvinylsilicone rubber (MVQ). The obtained results indicate that they can be successfully incorporated into silica-filled rubbers as modifying agents since they enhance cross-link density and improve most properties of the resulting network. It is also worth noting that the incorporation of POSS molecules resulted in stabilizing effect against adverse changes induced by the climatic, ozone or UV ageing of the rubbers. Furthermore, we obtained interesting results of rubbers surface modification using POSS functionalised with halogen groups (Cl, F, and Br). As the results, surface energy of the elastomeric composites and their hydrophobicity increased, barrier properties improved and thermal stability increased as well. Additionally, the studies with silicone rubber and POSS containing acidic and alkaline groups revealed composites with self-healing properties. The observed effects strictly depend on a kind and quantity of functional groups present in angles of POSS cages.

Keywords: elastomeric composites, POSS, properties modyfication, silicone rubber

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1287 Assessing Brain Targeting Efficiency of Ionisable Lipid Nanoparticles Encapsulating Cas9 mRNA/gGFP Following Different Routes of Administration in Mice

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

Abstract:

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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1286 Cooling With Phase-Change-Material in Vietnam: Outcomes at 18 Months

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

Abstract:

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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1285 Assessment of the Effect of Orally Administered Itopride on Gall Bladder Ejection Fraction by a Fatty Meal Cholescintigraphy in Patients with Diabetes

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

Abstract:

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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1284 Comparative Study between Mesenchymal Stem Cells and Regulatory T-Cells in Macrophage Polarization for Organ Transplant Tolerance: In Vitro Study

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

Abstract:

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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1283 Synthesis and Characterization of Fibrin/Polyethylene Glycol-Based Interpenetrating Polymer Networks for Dermal Tissue Engineering

Authors: O. Gsib, U. Peirera, C. Egles, S. A. Bencherif

Abstract:

In skin regenerative medicine, one of the critical issues is to produce a three-dimensional scaffold with optimized porosity for dermal fibroblast infiltration and neovascularization, which exhibits high mechanical properties and displays sufficient wound healing characteristics. In this study, we report on the synthesis and characterization of macroporous sequential interpenetrating polymer networks (IPNs) combining skin wound healing properties of fibrin with the excellent physical properties of polyethylene glycol (PEG). Fibrin fibers serve as a provisional biologically active network to promote cell adhesion and proliferation while PEG provides the mechanical stability to maintain the entire 3D construct. After having modified both PEG and Serum Albumin (used for promoting enzymatic degradability) by adding methacrylate residues (PEGDM and SAM, respectively), Fibrin/PEGDM-SAM sequential IPNs were synthesized as follows: Macroporous sponges were first produced from PEGDM-SAM hydrogels by a freeze-drying technique and then rehydrated by adding the fibrin precursors. Environmental Scanning Electron Microscopy (ESEM) and Confocal Laser Scanning Microscopy (CLSM) were used to characterize their microstructure. Human dermal fibroblasts were cultivated during one week in the constructs and different cell culture parameters (viability, morphology, proliferation) were evaluated. Subcutaneous implantations of the scaffolds were conducted on five-week old male nude mice to investigate their biocompatibility in vivo. We successfully synthesized interconnected and macroporous Fibrin/PEGDM-SAM sequential IPNs. The viability of primary dermal fibroblasts was well maintained (above 90%) after 2 days of culture. Cells were able to adhere, spread and proliferate in the scaffolds suggesting the suitable porosity and intrinsic biologic properties of the constructs. The fibrin network adopted a spider web shape that covered partially the pores allowing easier cell infiltration into the macroporous structure. To further characterize the in vitro cell behavior, cell proliferation (EdU incorporation, MTS assay) is being studied. Preliminary histological analysis of animal studies indicated the persistence of hydrogels even after one-month post implantation and confirmed the absence of inflammation response, good biocompatibility and biointegration of our scaffolds within the surrounding tissues. These results suggest that our Fibrin/PEGDM-SAM IPNs could be considered as potential candidates for dermis regenerative medicine. Histological analysis will be completed to further assess scaffold remodeling including de novo extracellular matrix protein synthesis and early stage angiogenesis analysis. Compression measurements will be conducted to investigate the mechanical properties.

Keywords: fibrin, hydrogels for dermal reconstruction, polyethylene glycol, semi-interpenetrating polymer network

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1282 Synthesis of Bismuth-Hyaluronic Acid Nanoparticles Containing Melittin Coated with Chitosan for Treating Eye Cancer Cells with Radiotherapy

Authors: Akbar Esmaeili, Fateme Dadashi

Abstract:

Bismuth can increase radiation and reduce the dose of radiotherapy. On the other hand, hyaluronic acid plays a role in healing damaged cells, and melittin has been used to destroy cancer cells. This research aims to destroy eye cancer cells and accelerate the recovery of damaged healthy cells during treatment. In this research, we used this nanoparticle, the sol-gel method. According to the optimization process that was carried out, we obtained the optimal value of the desired variables for the manufacture of nanoparticles. The advantage of doing this is reducing the amount of medicine used, as a result of reducing the number of side effects during the treatment and using melittin as an anti-eye cancer drug and the presence of hyaluronic acid to accelerate the recovery of cells, as well as coating the bismuth nanoparticle with chitosan to increase the half-life of the nanoparticle and prevent its adhesion.

Keywords: synthesis, nanoparticles, coated, cancer

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1281 Melting and Making Zn-Based Alloys and Examine Their Biodegradable and Biocompatible Properties

Authors: Abdulrahman Sumayli

Abstract:

Natural Zinc has many significant biological functions, including developments and sustainable of bones and wound healing. Metallic zinc has recently been explored as potential biomaterials that have preferable biodegradable, biocompatible, and mechanical properties. Pure metal zinc has a preferable physical and mechanical properties for biodegradable and biocompatible applications such as density and modulus of elasticity. The aim of the research is to make different Zn-based metallic alloys and test them effectively to be used as biocompatible and biodegradable materials in the field biomedical application. Microstructure study of the as-cast alloys will be examined using SEM (scanning electron microscope) followed by X-ray diffraction investigated so as to evaluate phase constitution of the designed alloys. After that, immersion test and electrochemical test will be applied to the designed alloys so as to study bio corrosion behaviour of the proposed alloys. Finally, in vitro cytocompatibility well conducted to study biocompatibility of the made alloys.

Keywords: Zn-based alloys, biodegradable and biocompatible materials, cytotoxicity test, neutron synchrotron imaging

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1280 The Cult of St. Agata as Cultural Mark of Heritage Community Resilience in Abruzzo (Italy, Central Apennine)

Authors: Carmen Soria

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The aim of this paper is the study of the cultural and anthropological consequences of the historical natural disasters in Abruzzo (Italy, Central Apennine). These events have left cultural marks in local traditions as well as mythological stories, specific cults, or sanctuary areas in apotropaic function to prevent catastrophic events. Despite the difficult to find archaeological evidence of natural disasters, neverthless, the analisys of micro placenames, directly or indirectly related to such events, represents an integrated and interdisciplinary approach between seismology studies and landscape analysis. Toponymic data, indeed, highlight the strong relation between geomorphological features of areas affected by natural disasters and heritage community resilience, such as, for example, the cult of St. Agatha, widespread in the nearby of healing spring-water and ancient caves as a place of worship, in continuity with pagan rituals.

Keywords: abruzzo, heritage community resilience, seismic planames, St. agata

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1279 Creating Inclusive Educational Environments for Women Faculty of Color Harnessing Ubuntu Perspectives

Authors: Gonzaga Mukasa, Faith Maina, Amani Zaier

Abstract:

This study investigated whether harnessing Ubuntu perspectives can aid in healing wounds Hierarchical Microaggressive intersectionalities inflict on African immigrant women faculty in predominantly white institutions. The study interviewed 8 African immigrant faculty from different higher education institutions in the United States selected using the snowball sampling technique. The Ubuntu Theory anchored the study. Findings indicated that women faculty of color experience Hierarchical Microaggressive intersectionalities leading them to lose job satisfaction and feel deprofessionalized and isolated. The recommendations were that institutions make their recruitment more inclusive of women of color to avoid isolation. And should embrace Ubuntu perspectives such as survival, solidarity, compassion, dignity, and mutual respect to architect educational environments that foster diversity and inclusion.

Keywords: ubuntu, women faculty, African immigrants, hierarchical microaggressive intersectionalities

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1278 Engineering a Tumor Extracellular Matrix Towards an in vivo Mimicking 3D Tumor Microenvironment

Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang

Abstract:

Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.

Keywords: cancer, extracellular matrix, hydrogel, microfluidic

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1277 Electrospinning of Nanofibrous Meshes and Surface-Modification for Biomedical Application

Authors: Hyuk Sang Yoo, Young Ju Son, Wei Mao, Myung Gu Kang, Sol Lee

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Biomedical applications of electrospun nanofibrous meshes have been received tremendous attentions because of their unique structures and versatilities as biomaterials. Incorporation of growth factors in fibrous meshes can be performed by surface-modification and encapsulation. Those growth factors stimulate differentiation and proliferation of specific types of cells and thus lead tissue regenerations of specific cell types. Topographical cues of electrospun nanofibrous meshes also increase differentiation of specific cell types according to alignments of fibrous structures. Wound healing treatments of diabetic ulcers were performed using nanofibrous meshes encapsulating multiple growth factors. Aligned nanofibrous meshes and those with random configuration were compared for differentiating mesenchymal stem cells into neuronal cells. Thus, nanofibrous meshes can be applied to drug delivery carriers and matrix for promoting cellular proliferation.

Keywords: nanofiber, tissue, mesh, drug

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1276 Biocompatible Hydrogel Materials Containing Cytostatics for Cancer Treatment

Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak

Abstract:

Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.

Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity

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