Search results for: proliferation

Authors: Małgorzata Drzewiecka, Tomasz Śliwiński, Maciej Radek

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The inhibition of histone deacetyles (HDACs) holds promise as a potential anti-cancer therapy because histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, histone deacetylase inhibitors (HDACi) such as class I HDAC inhibitor - valproic acid (VPA) have been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that, using of VPA in combination with talazoparib (BMN-637 – PARP1 inhibitor – PARPi) and/or Dacarabazine (DTIC - alkylating agent) resulted in increased DNA double strand break (DSB) and reduced survival (while not affecting primary melanocytes )and proliferation of melanoma cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-637. In addition, inhibition of HDAC caused sensitization of melanoma cells to dacarbazine and BMN-637 in melanoma xenografts in vivo. At the mRNA and protein level histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study provides that combining HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is known for being one of the most aggressive malignant tumors. The findings presented here point to a scenario in which HDAC via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.

Keywords: melanoma, hdac, parp inhibitor, valproic acid

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: Chieh-Chung Tsou, Chun-Min Lo, Yeh-Shiu Chu

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Cell’s mechanical forces provide important physical cues in regulation of proper cellular functions, such as cell differentiation, proliferation and migration. It is believed that adhesive forces generated by cell-cell interaction are able to transmit to the interior of cell through filamentous cortical cytoskeleton. Prominent among other membrane receptors, Cadherins are prototypical adhesive molecules able to generate remarkable forces to regulate intercellular adhesion. However, the mechanistic steps of mechano-transduction in Cadherin-mediated adhesion remain very controversial. We are interested in understanding how Cadherin protein complexes enable force generation and transmission at cell-cell contact in the initial stage of intercellular adhesion. For providing a better control of time, space, and substrate stiffness, in this study, a combination of protein micropattern, micropipette manipulation, and traction force microscopy is used. Pair micropattern with different forms confines cell spreading area and the gaps in pairs varied from 2 to 8 microns are applied for monitoring the forces that cell pairs generated, measured by traction force microscopy. Moreover, cell clones obtained from epithelial cells undergone genome editing are used to score the importance for known components of Cadherin complexes in force generation. We believe that our results from this combinatory mechanobiological method will provide deep insights on understanding the biophysical principle governing mechano- transduction of Cadherin-mediated intercellular adhesion.

Keywords: cadherin, intercellular adhesion, protein micropattern, traction force microscopy

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Authors: Zayedali Shaikh

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Increasingly now more than ever, UV damage brings with it a litany of minor deformities that can range from mild lesions and discoloring to cataracts and blindness. Pluripotent stem cells in planaria and human skin can be used to treat wounds and skin damage, with the primary limitations being inadequate growth factors. Photobiomodulation therapy in the form of low-intensity red light therapy has been proven to provide helpful benefits in the healing of skin that displays some of the symptoms of UV damage, such as burns and lesions, along with stimulating the proliferation of stem cells in recellularizing tissue. This paper puts forth an alternate means by which to treat the effects of UV damage using the freshwater planarian model system, Dugesia dorotocephala, known for its regenerative abilities and abundance of pluripotent stem cells, which allow for the rapid growth and repair of missing or damaged structures. Our work consisted of exposing planaria to different types of light: red light, blue light, white light, darkness, red and blue light together, UV light, and finally, red and UV light together. The primary focus of this research was on the red and UV lights, with six controls acting as metrics to compare our findings. Through computer-assisted morphological analysis, the results show that there is no significant difference in the rates of regeneration of planaria treated with simultaneous exposure to red and UV light versus planaria in darkness (p > .05), a representation of their preferred natural habitat. Our research suggests the viability of red-light therapy in actively combating UV damage and expediting the growth of epidermal stem cells by acting as another growth factor.

Keywords: regenerative medicine, stem cells, planaria, photobiomodulation

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Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan

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Objective: Bone marrow derived stem cells, endothelial progenitor cells (EPCs), protect against atherosclerotic vascular damage. However, EPCs are depleted in AS and contribute to the enhanced cardiovascular risk. Statins have a protective effect in CAD and diabetes by enhancing the proliferation, migration and survival of EPCs. Therapeutic potential of augmenting EPCs to treat the heightened cardiovascular risk of AS has not yet been exploited. We aimed to investigate the effect of rosuvastatin on EPCs population and inflammation in AS. Methods: 30 AS patients were randomized to receive 6 months of treatment with rosuvastatin (10 mg/day, n=15) and placebo (n=15) as an adjunct to existing stable anti-rheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Inflammatory measures (BASDAI, BASFI, CRP and ESR), pro-inflammatory cytokines (TNF-α, IL-6 and IL-1) and lipids were measured at baseline and after treatment. Results: At baseline, inflammatory measures and pro-inflammatory cytokines were elevated and EPCs depleted among both groups. EPCs increased significantly (p < 0.01) after treatment with rosuvastatin. At 6 months, BASDAI, BASFI, ESR, CRP, TNF-α, and IL-6 improved significantly in rosuvastatin group. Significant negative correlation was observed between EPCs and BASDAI, CRP and IL-6 after rosuvastatin treatment. Conclusion: First study to show that rosuvastatin augments EPCs population in AS. This defines a novel mechanism of rosuvastatin treatment in AS: the augmentation of EPCs with improvement in proinflammatory cytokines and inflammatory disease activity. The augmentation of EPCs by rosuvastatin may provide a novel strategy to prevent cardiovascular events in AS.

Keywords: ankylosing spondylitis, Endothelial Progenitor Cells, inflammation, pro-inflammatory cytokines, rosuvastatin

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Authors: Ayda Youssef, Mohammed Ali Khalaf, Tarek Rafaat

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Background: Langerhans cell histiocytosis (LCH) is a rare multi-systemic disease that shows an abnormal proliferation of these kinds of cells associated with a granular infiltration that affects different structures of the human body, including the lung, liver, spleen, lymph nodes, brain, mucocutaneous, soft tissue (head and neck), and salivary glands. Evaluation of the extent of disease is one of the major predictors of patient outcome. Objectives: To recognize the pathogenesis of Langerhans cell histiocytosis (LCH), describe the radiologic criteria that are suggestive of LCH in different organs rather than the bones and to illustrate the appropriate differential diagnoses for LCH in each of the common extra-osseous sites. Material and methods: A retrospective study was done on 150 biopsy-proven LCH patients from 2007 to 2012. All patients underwent imaging studies, mostly US, CT, and MRI. These patients were reviewed to assess the extra-skeletal manifestations of LCH. Results: In 150 patients with biopsy-proven LCH, There were 33 patients with liver affection, 5 patients with splenic lesions, 55 patients with enlarged lymph nodes, 9 patient with CNS disease and 11 patients with lung involvement. Conclusions: Because of the frequent LCH children and evaluation of the extent of disease is one of the major predictors of patient outcome. Radiologist need to be familiar with its presentation in different organs and regions of body outside the commonest site of affection (bones). A high-index suspicion should be raised a biopsy is recommended in the presence of radiological suspicion. Chemotherapy is the preferred therapeutic modality.

Keywords: langerhans cell histiocytosis, extra-skeletal, pediatrics, radiology

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Authors: Katerina Balounova, Jiri Pacha, Peter Ergang, Martin Vodicka, Pavlina Kvapilova

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MicroRNAs are small non-coding RNAs involved in a wide range of physiological processes. Post-transcriptional regulation of gene expression by microRNAs gives the organism a further level of control of the gene-expression program and the disruption of this microRNA regulatory mechanism seems to increase the risk of various pathophysiological conditions including tumorigenesis. To the present day, microRNAs were shown to participate in the mayor signalization pathways leading to tumorigenesis, including proliferation, cell cycle, apoptosis and metastasis formation. In addition, microRNAs have been found to play important roles in the generation and maintenance of circadian clock. These clocks generate circadian rhythms, which participate in a number of regulatory pathways. Disruption of the circadian signals seems to be associated with the development and the progression of tumours including colorectal cancer. We investigated therefore whether the diurnal profiles of miRNAs linked to tumorigenesis and regulation of circadian clock are changed during tumorigenesis. Based on published data we chose 10 microRNAs linked to tumorigenesis or circadian clock (let-7b-5p, miR 1 3p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p, miR 34a 5p and miR 93 5p) and compared their 24-hr expression profiles in healthy and in chemically induces primary colorectal tumours of 52week-old mice. Using RT-qPCR we proved circadian rhythmicity in let-7b-5p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p and miR 93 5p in healthy colon but not in tumours. The acrophases of miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p and miR 93 5p were reached around CT 24, the acrophases of let-7b-5p and miR-29a-3p were slightly shifted and reached around CT 21. In summary, our results show that circadian regulation of some colonic microRNAs is greatly affected by neoplastic transformation.

Keywords: circadian rhythm, colon, colorectal cancer, microRNA, tumorigenesis

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Authors: Boukhalfa Djemouai, Belkadi Souhila, Safsaf Boubakeur

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To increase the profitability of the national herd so that it can meet the needs of the population, Algeria has proceeded to the introduction of new reproductive biotechnologies, including artificial insemination on natural heat, by induction and heat synchronization. This biotechnology uses the male way for the creation and dissemination of genetic progress. The study has focused on 30 goat kids and bucks local breed aged between 03 and 24 months, divided into 03 groups 03-06 months[Grp 1; n=9], 07-10 months [Grp 2; n=13] and 11-24 months [Grp 3; n=8], in order to determine the influence of age on testicular evolution by measurements of testis and scrotum, and the epididymis sperm parameters evaluation. These parameters are influenced by age variations (sperm and spermocytogram). The examined parameters have focused on testicular weight (grams), the scrotal circumference (cm), mass mobility (%), vitality rate (%), sperm concentration (x 109), and percentage of abnormal spermatozoa (%). The ANOVA reveals a significance effect of age on parameters: testis weight, scrotal circumference, sperm concentration, motility varying between high (p < 0.01) to very high significance (p < 0.001), while in viability and abnormalities no significance was observed between all groups. The value of these parameters increased significantly until the age of 02 years, while that of sperm abnormalities has increased in Grp2. The histological study of testicular development shows that the genetic spermatozoa function characterized by cell proliferation, which is more and more intense starting from the age of 05 months and can be considered as an age of puberty in the local breed goat Arbia and increases with animal age.

Keywords: kids and bucks, epididymis sperm, testicular measurements, Arbia breed

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Authors: Amore Gerber, Gerrit Crafford

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This research paper explores the root causes of the shortage of professional electricians in the Eastern Cape, South Africa. The primary objectives are to identify the underlying reasons contributing to this deficit, analyze the consequences of the shortage, and propose practical solutions to address this critical issue. The research employed an interpretivist paradigm and an inductive approach. Qualitative data was gathered through semi-structured interviews with professional electricians working in the Eastern Cape. Thematic analysis was used to identify common themes and comprehensively understand the issue. The analysis revealed that the shortage of electricians can be attributed primarily to training challenges and a lack of awareness within the industry. This shortage has significant repercussions, as it has led to the proliferation of unqualified electricians, exacerbating the problem. The study identified two key solutions to address this issue: promoting education and trade programs and transforming electrical instruction and education. The research was conducted in the Eastern Cape and reflects the viewpoints of professional electricians. Results may differ in other locations or where the effects are investigated from a client’s perspective. The research uncovers the root causes of the electrician shortage and offers valuable insights for devising effective solutions to address these challenges. This paper adds a significant dimension to the current literature gap. The study's findings underscore deficiencies in awareness and training as fundamental factors driving the shortage of electricians, emphasizing the urgent need to address these issues to bridge the gap.

Keywords: electrician shortage, skill gap, training, awareness

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Authors: Charlene N. T. Mfangnia, Henri Tonnang, Berge Tsanou, Jeremy Herren

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The Microsporidia MB found in the populations of anopheles is a recently discovered symbiont responsible for the Plasmodium transmission blocking. From early studies, it was established that the symbiont can be transmitted vertically and horizontally. The present study uses compartmental mathematical modelling approach to investigate the dynamics of Microsporidia transmission in the mosquito population with the mindset of establishing a mechanism for use to control malaria. Data and information obtained from laboratory experiments are used to estimate the model parameters with and without temperature dependency of mosquito traits. We carry out the mathematical analysis focusing on the equilibria states and their stability for the autonomous model. Through the modelling experiments, we are able to assess and confirm the contribution of vertical and horizontal transmission in the proliferation of Microsporidia MB in the mosquito population. In addition, the basic and target reproductions are computed, and some long-term behaviours of the model, such as the local (and global) stability of equilibrium points, are rigorously analysed and illustrated numerically. We establish the conditions responsible for the low prevalence of the symbiont-infected mosquitoes observed in nature. Moreover, we identify the male death rate, the mating rate and the attractiveness of MB-positive mosquitoes as mosquito traits that significantly influence the spread of Microsporidia MB. Furthermore, we highlight the influence of temperature in the establishment and persistence of MB-infected mosquitoes in a given area.

Keywords: microsporidia MB, vertical transmission, horizontal transmission, compartmental modelling approach, temperature-dependent mosquito traits, malaria, plasmodium-transmission blocking

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Authors: E. Kalcheva, A. Taki, Y. Hadi

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High-rises and placemaking is an understudied combination which receives more and more interest with the proliferation of this typology in many British cities. The reason for studying three major cities in England: London, Birmingham and Manchester, is to learn from the latest advances in urban design in well-developed and prominent urban environment. The analysis of several high-rise sites reveals the weaknesses in urban design of contemporary British cities and presents an opportunity to study from the implemented examples. Therefore, the purpose of this research is to analyze design approaches towards creating a sustainable and varied urban environment when high-rises are involved. The research questions raised by the study are: what is the quality of high-rises and their surroundings; what facilities and features are deployed in the research area; what is the role of the high-rise buildings in the placemaking process; what urban design principles are applicable in this context. The methodology utilizes observation of the researched area by structured questions, developed by the author to evaluate the outdoor qualities of the high-rise surroundings. In this context, the paper argues that the quality of the public realm around the high-rises is quite low, missing basic but vital elements such as plazas, public art, and seating, along with landscaping and pocket parks. There is lack of coherence, the rhythm of the streets is often disrupted, and even though the high-rises are very aesthetically appealing, they fail to create a sense of place on their own. The implications of the study are that future planning can take into consideration the critique in this article and provide more opportunities for urban design interventions around high-rise buildings in the British cities.

Keywords: high-rises, placemaking, urban design, townscape

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Authors: Jin Boo Jeong

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In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β–catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A3B03931713).

Keywords: anticancer, calyx of persimmon, cyclin D1, Diospyros kaki Thunb., human colorectal cancer

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Authors: Vidhula Ahire, Amit Kumar, K. P. Mishra, Gauri Kulkarni

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Herbal polyphenols have gained significance because of their increasing promise in prevention and treatment of cancer. Therefore, development of a dietary compound as an effective radiosensitizer and a radioprotector is highly warranted for cervical cancer patients undergoing therapy. This study describes the cytotoxic effects of the flavonoid, ellagic acid (EA) when administered either alone or in combination with gamma radiation on cervical cancer HeLa cells in vitro. Apoptotic index and proliferation were measured by using trypan blue assay. Reproductive cell death was analyzed by clonogenic assay. Propidium iodide staining for flowcytometry was performed to analyze cell cycle modulation. Nuclear and mitochondrial changes were studied with specific dyes. DNA repair kinetics was analyzed by immunofluorescence assay. Evaluation and comparison of EA effects were performed with other clinically used breast cancer drugs. When tumor cells were exposed to 2 and 4 Gy of irradiation in presence of EA (10 μM), it yielded a synergistic cytotoxic effect on cervical cancer cells whereas in NIH3T3 cells it reversed the injury caused by irradiation and abetted in the regaining of normal healthy cells. At 24h ~25foci/cell was observed and 2.6 fold decrease in the mitochondrial membrane potential. Up to 40% cell were arrested in the G1 phase and 20-36% cells exhibited apoptosis. Our results demonstrate the role of increased apoptosis and cell cycle modulation in the mechanism of EA mediated radiosensitization of cervical cancer cells and thus advocating EA as an adjuvant for preclinical trials in cancer chemo- radiotherapy.

Keywords: cervical cancer, ellagic acid, sensitization, radiation therapy

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Authors: Jyotsna Gupta, S. Ghosh, S. Aravindan

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The requirement of artificial prostheses (such as hip and knee joints) has increased with time. Many researchers are working to develop new implants with improved properties such as excellent biocompatibility with no tissue reactions, corrosion resistance in body fluid, high yield strength and low elastic modulus. Further, the morphological properties of the artificial implants should also match with that of the human bone so that cell adhesion, proliferation and transportation of the minerals and nutrition through body fluid can be obtained. Present study attempts to make porous Ti6Al15Mo alloys through powder metallurgy route using space holder technique. The alloy consists of 6wt% of Al which was taken as α phase stabilizer and 15wt% Mo was taken as β phase stabilizer with theoretical density 4.708. Ammonium hydrogen carbonate is used as a space holder in order to generate the porosity. The porosity of these fabricated porous alloys was controlled by adding the 0, 50, 70 vol.% of the space holder content. Three phases were found in the microstructure: α, α_2 and β phase of titanium. Kirkendall pores are observed to be decreased with increase of holding time during sintering and parallelly compressive strength and elastic modulus value increased slightly. Compressive strength and elastic modulus of porous Ti-6Al-15Mo alloy (1.17 g/cm3 density) is found to be suitable for cancellous bone. Released ions from Ti-6Al-15Mo alloy are far below from the permissible limits in human body.

Keywords: bone implant, powder metallurgy, sintering time, Ti-6Al-15Mo

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Authors: Anne McCarthy, Anna Kim, Yin Song, Kyoo Jo, Donald Cropek, Sungmin Hong

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Corrosion prevention remains an indispensable concern across a spectrum of industries, demanding inventive and adaptable methodologies to effectively tackle the ever-evolving obstacles presented by corrosive surroundings. This abstract introduces a pioneering approach to corrosion prevention that amalgamates the distinct attributes of magneto-responsive polymers with finely adjustable hydrophobicity inspired by the structure of cicada wings, effectively deterring bacterial proliferation and biofilm formation. The proposed strategy entails the creation of an innovative array of magneto-responsive nanostructures endowed with the capacity to dynamically modulate their hydrophobic characteristics. This dynamic control over hydrophobicity facilitates active repulsion of water and corrosive agents on demand. Additionally, the cyclic motion generated by magnetic activation prevents the biofilms formation and rejection. Thus, the synergistic interplay between magneto-active nanostructures and hydrophobicity manipulation establishes a versatile defensive mechanism against diverse corrosive agents. This study introduces a novel method for corrosion prevention, harnessing the advantages of magneto-active nanostructures and the precision of hydrophobicity adjustment, resulting in water-repellency, effective biofilm removal, and offering a promising solution to handle corrosion-related challenges. We believe that the combined effect will significantly contribute to extending asset lifespan, improving safety, and reducing maintenance costs in the face of corrosion threats.

Keywords: magneto-active material, nanoimprinting, corrosion prevention, hydrophobicity

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Authors: H. Trabelsi, A. Chehma, I. Benseddik

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Animals can play an important role in the seed dispersal cycle through the active or passive uptake of seeds and the subsequent external (epizoochory) or internal transport (endozoochory) of seeds. In Algeria, small ruminants and camels are generally conducted in extensive livestock exploiting the Saharan and steppe rangelands. To get an idea on the ecological potential role of these animals in the spontaneous plants proliferation, we propose to make a study of seeds dispersal and germination possibilities by camel faeces compared to those of small ruminants. Manual faeces decortication of the two animals categories has allowed to inventory 72 seed which 71% are in good condition, while 29% of the seeds that are encountered are partially altered and could not be identified. The species that have been identified, from small ruminants dung are weeds of cultures, while those identified from camel dung are spontaneous plants of Saharan rangeland. Concerning germination in the laboratory, only 3 species seeds were germinated from camel feces, whose germination rate varies from 25% to 100%. Contrary to Sheep-Goat feces, a single species germinated with 71%. The three months seed germination in greenhouse allowed to identify 10 species belonging to 4 botanical families (5 species from small ruminants dung and 3 species from Camel dung). In general, the results show the positive effect played by two animals categories for plants seed dispersal with the camel particularity for spontaneous plants due to its capacity to cover long distances in different rangeland types.

Keywords: Algeria, camel, endozoochory, seeds, sheep-goat, rangeland

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Authors: Daniel Canales, Fabián Alvarez, Pablo Varela, Marcela Saavedra, Claudio García, Paula Zapata

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Calcium oxide nanoparticles (n-CaO) ca. 8 nm were obtained from eggshell waste. The n-CaO was incorporated into Poly(lactic acid) PLA matrix in 10 and 20 wt.% of filler content by electrospinning process to obtain PLA/n-CaO nanocomposite fibers as a potential use in scaffold for bone tissue regeneration. The fibers morphology and diameter were homogeneity, the PLA had a diameter of 2.2 ± 0.8 µm and, with the nanoparticles incorporation (20wt.%), reached ca. 2.9 ± 0.9 µm. The PLA/n-CaO nanocomposites fibers showed in vitro bioactivity, capable of inducing the precipitation of hydroxyapatite (HA) layer in the fiber surface after 7 days in Simulated Body Solution (SBF). The biocidal and biological properties of PLA/n-Cao with 20 wt.% were evaluated, showing a 30% reduction in bacterial viability against S. aureus and 11% for E. coli after 6 hours of bacterial suspensions exposure. Furthermore, the fibers did not show a cytotoxic effect on the bone marrow ST-2 cell line, permitting the cell adhesion and proliferation in Roswell Park Memorial Institute medium (RPMI). The PLA/n-CaO with 20 wt.% of nanoparticles showed a higher capacity to promote the osteogenic differentiation, significantly increasing the alkaline phosphatase (ALP) expression after 7 days compared to PLA and cell control. The in vivo analysis corroborated the biocompatibility of scaffolds prepared, the presence of n-CaO in PLA reduced the formation of fibrous encapsulation of the material improve the healing process.

Keywords: electrospun scaffolds, PLA based nanocomposites, calcium oxide nanoparticles, bioactive materials, tissue engineering

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Authors: Abosede Ijabadeniyi, Jeevarathnam P. Govender

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Prevailing strategic Corporate Social Responsibility (CSR) research is predominantly centred around the predictive implications of the construct on behavioural outcomes. This phenomenon limits the depth of our understanding of the trajectory of strategic CSR. The purpose of this paper is to investigate the mediating effects of CSR expectations on the relationship between consumer value and purchase behaviour by identifying the implications of the multidimensionality of CSR (economic, legal, ethical and philanthropic) on the latter. Drawing from the stakeholder theory and its interplay with the prevalence of Ubuntu values; the underlying force which governs the values of South African camaraderie, we hypothesise that the multidimensionality of CSR expectations has positive mediating effects in the relationship between consumer value and purchase behaviour. Partial Least Square (PLS) path modelling was employed, using six measures of the average path coefficient (APC) to test the relationship between the constructs. Results from a sample of mall shoppers of (n=411), based on a survey conducted across five major malls in Durban, South Africa, indicate that only the legal dimension of CSR serves as a mediating factor in the relationship among the constructs. South Africa’s unique history of segregation, leading to the proliferation of spontaneous organisational approach to CSR and higher expectations of organisational legitimacy are identified as antecedents of consumers’ reliance on the law (legal CSR) to redress the ills of the past, sustainable development, and socially responsible behaviour. The paper also highlights theoretical and managerial implications for future research.

Keywords: consumer value, corporate marketing, corporate social responsibility, purchase behaviour, Ubuntu

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Authors: Doaa M. Elghannam, Nashwa Khayrat Abousamra, Doaa A. Shahin, Enas F. Goda, Hanan Azzam, Emad Azmy, Manal Salah El-Din

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Background: The pathogenesis of acute myeloid leukemia (AML) involves the cooperation of mutations promoting proliferation/survival and those impairing differentiation. Point mutations of the NRAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). Aim: The present work was conducted to study the frequency and prognostic significance of NRAS gene mutations (NRASmut) in de novo Egyptian adult AML. Material and methods: Bone marrow specimens from 150 patients with de novo acute myeloid leukemia and controls were analyzed by genomic PCR-SSCP at codons 12, 13 (exon 1), and 61 (exon 2) for NRAS mutations. Results: NRAS gene mutations was found in 19/150 (12.7%) AML cases, represented more frequently in the FAB subtype M4eo (P = 0.028), and at codon 12, 13 (14of 19; 73.7%). Patients with NRASmut had a significant lower peripheral marrow blasts (P = 0.004, P=0.03) and non significant improved clinical outcome than patients without the mutation. Complete remission rate was (63.2% vs 56.5%; p=0.46), resistant disease (15.8% vs 23.6%; p=0.51), three years overall survival (44% vs 42%; P = 0.85) and disease free survival (42.1% vs 38.9%, P = 0.74). Multivariate analysis showed that age was the strongest unfavorable factor for overall survival (relative risk [RR], 1.9; P = .002), followed by cytogenetics (P = .004). FAB types, NRAS mutation, and leukocytosis were less important. Conclusions: NRAS gene mutation frequency and spectrum differ between biologically distinct subtypes of AML but do not significantly influence prognosis and clinical outcome.

Keywords: NRAS Gene, egyptian adult, acute myeloid leukemia, cytogenetics

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Authors: Saidou Hassidou, Laminou Ary Mahaman Moustapha

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Uncontrolled urbanization of African cities, plus the lack of municipal waste management services in these cities, generate landscapes become places of multiple and varied interactions between health and environment. In this sense, under strong urban growth in a context of sub-equipment sanitation, the city of Maradi doesn’t escape to this situation which results in the spread of pollution (release of unpleasant odors, proliferation of mosquitoes) and many diseases posing multiple health problems. Our study focuses only on liquid waste especially domestic wastewater. To study the different domestic wastewater management options in the town of Maradi, a survey was conducted among 340 households in 17 districts. We note in most cases a crucial of waste management infrastructure (drainage and wastewater treatment) at the city. Thus, only the individual sanitation facilities are used. In the town of Maradi, in addition to the storm drains, there are, in old districts, ditches that discharge wastewater and unfortunately end up in rivers without treatment. Domestic wastewater total production is estimated at 86,761.28 m3 per day. This water is mostly from laundry activities, bathing, dishes, and is discharged in large part through the streets, by more than 60% of households. Also, pit emptying is performed at 39.11% by the vehicle Peugeot tank. The quality of service rendered by an actor is very important to encourage households to join. Existing autonomous sanitation facilities are poorly designed and poorly maintained. Fecal sludge is dumped in a hole near saturated latrines; this work is mainly done by manual scavengers or dumped in fields or on nearby vacant land concessions.

Keywords: management, urban wastewater, domestic wastewater, Maradi, Niger

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Authors: Negar Zaheddoust, Negin Zaheddoust, Abbas Asoudeh-Fard

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Probiotic bacteria have been employed as a novel and less side-effect strategy for anticancer therapy. Since the oral cavity is a host for probiotic and pathogen bacteria to colonize, more investigation is needed to evaluate the effectiveness of this novel adjunctive treatment for oral cancer. We considered Lactobacillus plantarum as a probiotic and Streptococcus mutans as a pathogen bacterium in our study. The aim of this study is to examine the effect of Lactobacillus plantarum and Streptococcus mutans on Casp3, AKT / PTEN, and MAPK signaling pathway, which is involved in apoptosis or survival of oral cancer KB cells. On the other hand, to study the effects of these bacteria on normal cells, we used HUVEC cells. The KB and HUVEC cell lines were co-cultured with Lactobacillus plantarum and Streptococcus mutans isolated from traditional Iranian dairy and dental plaque, respectively. The growth-inhibitory effects of these two bacteria on KB and HUVEC cells were determined by (3-(4, 5-dimethylthiazolyl-2)-2,5diphenyltetrazolium bromide) MTT assay. MTT results demonstrated that the proliferation of KB cells was affected in a time, dose, and strain-dependent manner. In the following, the examination of induced apoptosis or necrosis in co-cultured KB cells with the best IC50 concentration of the Lactobacillus plantarum and Streptococcus mutans will be analyzed by FACS flow cytometry, and the changes in gene expression of Casp3, AKT / PTEN, MAPK genes will be evaluated using real-time polymerase chain reaction.

Keywords: cancer therapy, induced apoptosis, oral cancer, probiotics

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Authors: A. Reum Son, Jin Seon Kwon, Seung Hun Park, Hai Bang Lee, Moon Suk Kim

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These days, stem cell therapy is focused on for promising source of treatment in clinical human disease. As a supporter of stem cells, in situ-forming hydrogels with growth factors and cells appear to be a promising approach in tissue engineering. To examine osteogenic differentiation of hTMSCs which is one of mesenchymal stem cells in vivo in an injectable hydrogel, we use a methoxy polyethylene glycol-polycaprolactone blockcopolymer (MPEG-PCL) solution with osteogenic factors. We synthesized MPEG-PCL hydrogel and measured viscosity to check sol-gel transition. In order to demonstrate osteogenic ability of hTMSCs, we conducted in vitro osteogenesis experiment. Then, to confirm the cell cytotoxicity, we performed WST-1 with hTMSCs and MPEG-PCL. As the result of in vitro experiment, we implanted cell and hydrogel mixture into animal model and checked degree of osteogenesis with histological analysis and amount of expression genes. Through these experimental data, MPEG-PCL hydrogel has sol-gel transition in temperature change and is biocompatible with stem cells. In histological analysis and gene expression, hTMSCs are very good source of osteogenesis with hydrogel and will use it to tissue engineering as important treatment method. hTMSCs could be a good adult stem cell source for usability of isolation and high proliferation. When hTMSCs are used as cell therapy method with in situ-formed hydrogel, they may provide various benefits like a noninvasive alternative for bone tissue engineering applications.

Keywords: injectable hydrogel, stem cell, osteogenic differentiation, tissue engineering

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Authors: Derejaw Lake Melie, Alemu Kumlachew Tegegne

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The increasing prevalence of social media in Ethiopia has exacerbated societal challenges by fostering the proliferation of negative emotional posts and comments. Illicit use of social media has further exacerbated divisions among the population. Addressing these issues through manual identification and aggregation of emotions from millions of users for swift decision-making poses significant challenges, particularly given the rapid growth of Amharic language usage on social platforms. Consequently, there is a critical need to develop an intelligent system capable of automatically detecting and categorizing negative emotional content into social, religious, and political categories while also filtering out toxic online content. This paper aims to leverage sentiment analysis techniques to achieve automatic detection and filtering of negative emotional content from Amharic social media texts, employing a comparative study of deep learning algorithms. The study utilized a dataset comprising 29,962 comments collected from social media platforms using comment exporter software. Data pre-processing techniques were applied to enhance data quality, followed by the implementation of deep learning methods for training, testing, and evaluation. The results showed that CNN, GRU, LSTM, and Bi-LSTM classification models achieved accuracies of 83%, 50%, 84%, and 86%, respectively. Among these models, Bi-LSTM demonstrated the highest accuracy of 86% in the experiment.

Keywords: negative emotion, emotion detection, social media filtering sentiment analysis, deep learning.

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Authors: Yusser Olguín, Diego Benavente, Fernando Dorta, Nicole Orellana, Cristian Acevedo

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One of the greatest challenges of tissue engineering is the generation of materials in which the highest possible number of conditions can be incorporated to stimulate the proliferation and differentiation of cells, which will be transformed together with the material into new functional tissue. In this sense, considering the properties of microfluidics and its relationship with cellular micro-environments, the possibility of controlling flow patterns and the ability to design diverse patterns in the chips, a microfluidic cell culture system can be established as a means for the evaluation of the effect of different parameters in a controlled and precise manner. Specifically in relation to the study and development of alternatives in peripheral nervous tissue engineering, it is necessary to consider different physical and chemical neurotrophic stimuli that promote cell growth and differentiation. Chemical stimuli include certain vitamins, glucocorticoids, gangliosides, and growth factors, while physical stimuli include topological stimuli, mechanical forces of the cellular environment and electrical stimulation. In this context, the present investigation shows the results of cell stimulation in a microbioreactor using electrical and chemical stimuli, where the differentiation of PC12 cells as a neuronal model is evidenced by neurite expression, dependent on the stimuli and their combination. The results were analysed with a multi-factor statistical approach, showing several relationships and dependencies between different parameters. Chip design, operating parameters and concentrations of neurotrophic chemical factors were found to be preponderant, based on the characteristics of the electrical stimuli.

Keywords: microfluidics, nerve tissue engineering, microbioreactor, electrical stimuli

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Authors: Mario Spremic

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Despite the financial crisis and ongoing need for cost cutting, companies all around the world heavily invest in information systems (IS) and underlying information technology (IT). Information systems (IS) play very important role in modern business organizations supporting its organizational efficiency or, under certain circumstances, fostering business model innovation and change. IS can influence organization competitiveness in two ways: supporting operational efficiency (IS as a main infrastructure for the current business), or differentiating business through business model innovation and business process change. In either way, IS becomes very important to the business and needs to be aligned with strategic objectives in order to justify massive investments. A number of studies showed that investments in IS and underlying IT resulted in added business value if they are truly connected with strategic business objectives. In that sense proliferation of governance of enterprise IT helps companies manage, or rather, governs IS as a primary business function with executive management involved in making a decision about IS and IT. The quality of IT governance is rising with the large number of decisions about IS made by executive management, not IT departments. The more executive management is engaged in making a decision about IS and IT, the IT governance is of better quality. In this paper, the practice of governing the enterprise IT will be investigated on a sample of the largest 100 Croatian companies. Research questions posed here will reveal if there are some formal IT governance mechanisms, are there any differences in perceived role of IS and IT between CIOs (Chief Information Officers) and CEOs (Chief Executive Officers) of the sampled companies and what are the mechanisms to govern massive investment in enterprise IT.

Keywords: IT governance, governance of enterprise IT, information system auditing, operational efficiency

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Authors: Ismail Celik, Gulgun Ayhan Kilcigil, Berna Guven, Zumra Kara, Arzu Onay-Besikci

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Epidermal Growth Factor Receptor is the cell-surface receptor of the ErbB (erythroblastic leukemia viral oncogene homologue receptors) family of tyrosine kinases. It plays a vital role in regulating the proliferation and differentiation of cells. However, a variety of mechanisms, such as EGFR expression, mutation, and ligand-dependent receptor dimerization, are associated with the development of various activated EGFR tumors. EGFR is highly expressed in most solid tumors, including breast, head and neck cancer, non-small cell lung cancer (NSCLC), renal, ovarian, and colon cancers. Thus, specific EGFR inhibition plays one of the key roles in cancer treatment. The compounds used in the treatment as tyrosine kinase inhibitors are known to contain the benzimidazole isosterium indole, pazopanib, and axitinibin indazole rings. In addition, benzimidazoles have been shown to exhibit protein kinase inhibitory activity in addition to their different biological activities.Based on these data, it was planned and synthesized of some oxadiazole bearing benzimidazole derivatives [N-cyclohexyl-5-((2-phenyl/substitutedphenyl-1H-benzo[d]imidazole-1-yl) methyl)-1,3,4-oxadiazole-2-amine]. EGFR kinase inhibitory efficiency of the synthesized compounds was determined by comparing them with a known kinase inhibitor erlotinib in vitro, and two of the compounds bearing phenyl (19a) and 3,4-dibenzyloxyphenyl (21a) ring exhibited significant activities.

Keywords: benzimidazole, EGFR kinase inhibitory, oxadiazole, synthesis

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Authors: Harish Rajak, Kamlesh Raghuwanshi

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Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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Authors: Taurai T. Chikotie, Bruce W. Watson

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The manifestation of ‘new’ infectious diseases and the re-emergence of ‘old’ infectious diseases now present global problems and Southern Africa has not been spared from such calamity. Although having an organized public health system, countries in this region have failed to leverage on the proliferation in use of Information and Communication Technologies to promote effective disease surveillance. Objective: The objective of this study was to critically review and analyse the crucial variables to consider in the development and implementation of electronic disease surveillance systems in public health within the context of Southern Africa. Methodology: A critical review of literature published in English using, Google Scholar, EBSCOHOST, Science Direct, databases from the Centre for Disease Control (CDC and articles from the World Health Organisation (WHO) was undertaken. Manual reference and grey literature searches were also conducted. Results: Little has been done towards harnessing the potential of information technologies towards disease surveillance and this has been due to several challenges that include, lack of funding, lack of health informatics experts, poor supporting infrastructure, an unstable socio-political and socio-economic ecosystem in the region and archaic policies towards integration of information technologies in public health governance. Conclusion: The Southern African region stands to achieve better health outcomes if they adopt the use of e-disease surveillance systems in public health. However, the dynamics and complexities of the socio-economic, socio-political and technical variables would need addressing to ensure the successful development and implementation of e-disease surveillance systems in the region.

Keywords: critical review, disease surveillance, public health informatics, Southern Africa

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Authors: Zanib Nafees, Amir Razaghizad, Ibtisam Mahmoud, Abhinav Sharma, Renzo Cecere

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More than one million surgeries are performed each year in Canada, resulting in more than 100,000 associated serious adverse events (SAEs) per year. These are defined as unintended injuries or complications that adversely affect the well-being of patients. In recent years, there has been a proliferation of digital health interventions that have the potential to assist, monitor, and educate patients—facilitating self-care following post-operative discharge. Among digital health, interventions are interactive-voice response technologies (IVRs), which have been shown to be highly effective in certain medical settings. Although numerous IVR-based interventions have been developed, their effectiveness and utility remain unclear, notably in post-operative settings. To the best of our knowledge, no systematic or scoping reviews have evaluated this topic to date. Thus, the objective of this scoping review protocol is to systematically map and explore the literature and evidence describing and examining IVR tools, implementation, evaluation, outcome, and experience for post-operative patients. The focus will be primarily on the evaluation of baseline performance status, clinical assessment, treatment outcomes, and patient management, including self-management and self-monitoring. The objective of this scoping review is to assess the extent of the literature to direct future research efforts by identifying gaps and limitations in the literature and to highlight relevant determinants of positive outcomes in the emerging field of IVR monitoring for health outcomes in post-operative patients.

Keywords: digital healthcare technologies, post-surgery, interactive voice technology, interactive voice response

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Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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