Search results for: therapeutic jurisprudence

Authors: Emad A. Shalaby

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Cancer is a disease that causes abnormal cell proliferation and invades nearby tissues. Lung cancer is the second most frequent cancer worldwide. Natural anti-cancer drugs have been developed with low side effects and toxicity. Citrus peels and extracts have been demonstrated to have significant pharmacological and physiological effects as a result of the high concentration of phenolic compounds found in citrus fruits, particularly peels. Tangerine peels can serve as an effective source of bioactive substances such as phenolics, flavonoids, and catechins, which have antioxidant, antibacterial, anticancer, and anti-inflammatory properties. Consequently, this work aims to determine the anticancer activity of ethanol extract of Tangerine peels against the A549 cell line and identify the phenolic compound profile (19 compounds) by using HPLC. Anticancer and antioxidant potentials of the extract were evaluated by MTT assay and TLC- TLC-bioautography sprayed with DPPH reagent, respectively. The obtained results revealed that tangerine peel extract showed significant activity against the A549 cell line with IC50 of 97.66 μg/mL. HPLC analysis proved that the highest concentration is naringenin 464.05 mg/g. More studies indicate that naringenin has significant anticancer potential on A549 cancer cells. The results showed that naringenin binds t0 EGFR protein in A549 with high binding affinity and thus may reduce lung cancer cell migration and enhance the apoptosis of cancer cells. From the obtained results it could be concluded that tangerine peel extract is an effective anti-cancer agent that may potentially serve as a natural therapeutic option for lung cancer treatment.

Keywords: tangerine peel, A549 cell line, anticancer, naringenin, HPLC analysis, naringenin, TLC bioautography

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Authors: Abhay Asthana, Shally Toshkhani, Gyati Shilakari

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The present research was aimed to develop a biodegradable dermal patch formulation for wound healing in a novel, sustained and systematic manner. The goal is to reduce the frequency of dressings with improved drug delivery and thereby enhance therapeutic performance. In present study optimized formulation was designed using component polymers and excipients (e.g. Hydroxypropyl methyl cellulose, Ethylcellulose, and Gelatin) to impart significant folding endurance, elasticity and strength. Gelatin was used to get a mixture using ethylene glycol. Chitosan dissolved in suitable medium was mixed with stirring to gelatin mixture. With continued stirring to the mixture Curcumin was added in optimized ratio to get homogeneous dispersion. Polymers were dispersed with stirring in final formulation. The mixture was sonicated casted to get the film form. All steps were carried out under under strict aseptic conditions. The final formulation was a thin uniformly smooth textured film with dark brown-yellow color. The film was found to have folding endurance was around 20 to 21 times without a crack in an optimized formulation at RT (23C). The drug content was in range 96 to 102% and it passed the content uniform test. The final moisture content of the optimized formulation film was NMT 9.0%. The films passed stability study conducted at refrigerated conditions (4±0.2C) and at room temperature (23 ± 2C) for 30 days. Further, the drug content and texture remained undisturbed with stability study conducted at RT 23±2C for 45 and 90 days. Percentage cumulative drug release was found to be 80% in 12 h and matched the biodegradation rate as drug release with correlation factor R2 > 0.9. The film based formulation developed shows promising results in terms of stability and release profiles.

Keywords: biodegradable, patch, bioactive, polymer

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Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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Authors: Azza EL-Medany, Jamila EL-Medany

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Lung fibrosis is a common side effect of the chemotherapeutic agent, bleomycin. Current evidence suggests that reactive oxygen species may play a key role in the development of lung fibrosis. The present work studied the effect of green tea extract on bleomycin–induced lung fibrosis in rats. Animals were divided into three groups: (1) Saline control group; (2) bleomycin group in which rats were injected with bleomycin (15mg/kg,i.p.) three times a week for four weeks; (3) bleomycin and green tea group in which green tea extract was given to rats (100mg/kg/day, p.o) a week prior to bleomycin and daily during bleomycin injections for 4 weeks until the end of the experiment. Bleomycin–induced pulmonary injury and lung fibrosis that was indicated by increased lung hydroxyproline content, elevated nitric oxide synthase, myeoloperoxidase (MPO), platelet activating factor (PAF), tumor necrosis factor α (TNF_α), transforming growth factor 1β (TGF1β) and angiotensin converting enzyme (ACE) activity in lung tissues. On the other hand, bleomycin induced a reduction in reduced glutathione concentration (GSH). Moreover, bleomycin resulted in a severe histological changes in lung tissues revealed as lymphocytes and neutrophils infiltration, increased collagen deposition and fibrosis. Co-administration of bleomycin and green tea extract reduced bleomycin–induced lung injury as evaluated by the significant reduction in hydroxyproline content, nitric oxide synthase activity, levels of MPO, PAF, TNF-α, and ACE in lung tissues. Furthermore, green tea extract ameliorated bleomycin– induced reduction in GSH concentration. Finally, histological evidence supported the ability of green tea extract to attenuate bleomycin–induced lung fibrosis and consolidation. Thus, the finding of the present study provides that green tea may serve as a novel target for potential therapeutic treatment of lung fibrosis.

Keywords: bleomycin, lung fibrosis, green tea, oxygen species

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Authors: Kabange Kasumbwe, Viresh Mohanlall, Bharti Odhav, Venu Narayanaswamy

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Coumarins are naturally occurring plant metabolites known for their pharmacological properties such as anticoagulant, antimicrobial, anticancer, antioxidant, anti-inflammatory and antiviral properties. The pharmacological and biochemical properties and curative applications of coumarins depend on the substitution around the coumarin core structure. In the present study, seven halogenated coumarins CMRN1-CMRN7 were synthesized and evaluated for their anticancer activity. The cytotoxicity potential of the test compounds was evaluated against UACC62 (Melanoma), MCF-7 (Breast cancer) and PBM (Peripheral Blood Mononuclear) cell lines using MTT assay keeping doxorubicin as standard drug. The apoptotic potential of the coumarin compounds was evaluated against UACC62 (Melanoma) cell by assessing their morphological changes, membrane change, mitochondria membrane potential; pro-apoptotic changes were investigated using the AnnexinV-PI staining, JC-1, caspase-3 enzyme kits respectively on flow cytometer. The synthetic coumarin has strongly suppressed the cell proliferation of UACC-62 (Melanoma) and MCF-7 (Breast) Cancer cells, the higher toxicity of these compounds against UACC-62 (Melanoma) and MCF-7 (Breast) were CMRN3, CMRN4, CMRN5, CMRN6. However, compounds CMRN1, CMRN2, and CMRN7 had no significant inhibitory effect. Furthermore the active compounds CMRN3, CMRN4, CMRN5, CMRN6 exerted antiproliferative effects through apoptosis induction against UACC-62 (Melanoma), suggesting their potential could be considered as attractive lead molecules in the future for the development of potential anticancer agents since one of the important criteria in the development of therapeutic drugs for cancer treatment is to have high selectivity and less or no side-effects on normal cells and these compounds had no inhibitory effect against the PBMC cells.

Keywords: coumarin, MTT, apoptosis, cytotoxicity

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Authors: Tabussam Tufail

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Purpose: The core purpose of the current review article is to elaborate the phytochemicals present in turnip (brassica rapus l.) and also allied health claims. Plant-based foods contain a significant amount of bioactive compounds which provide desirable health benefits beyond the basic nutrition. Epidemiological evidence suggests that consumption of a diet rich in vegetables and fruits has positive implications for human health. Design: Potential of turnip peroxidase (TP) for the treatment of phenolic-contaminated solutions has been reviewed. However, issues of taste along with behavioral nutrition ought to be considered. So in the last decades, special attention has been paid towards edible plants, especially those that are rich in secondary metabolites (frequently called phytochemicals) and nowadays, there is an increasing interest in the antioxidant activity of such phytochemicals present in the diet. These chemicals favor nutritional and phytotherapy that is emerging as new concepts of health aid in recent years. Turnip is rich in these valuable ingredients though it can be employed as having health promoting and healing properties. Findings: Numerous bioactive components i.e. organic acids, phenolic compounds, turnip peroxidase, kaempeferol, vitamin-K, etc. are present in turnip. The review focused on the significance of plant derived (especially turnip) phenolic compounds as a source of certain beneficial compounds for human health. Owing to the presence of bioactive moieties, the turnip has high antioxidant activity, positive role in blood clotting, effectual in phenobarbital-induced sleeping time, effective against hepatic injury in diabetics and also have a good hepatoprotective role. Strong recommendations for consumption of nutraceuticals from turnip have become progressively popular to improve health, and to prevent from diseases.

Keywords: phytochemicals, turnip, antioxidants, health benefits

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Authors: Jyoti Kumari, Pavuluri Srinivasa Rao

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Jackfruit (ArtocarpusheterophyllusL.) is an underutilized yet highly nutritious fruit with unique flavour, known for its therapeutic and culinary properties. Fresh jackfruit bulb has a very short shelf life due to high moisture and sugar content leading to microbial and enzymatic browning, hindering its consumer acceptability and marketability. An attempt has been made for the preservation of the ripe jackfruit bulbs, by the application of high pressure (HP) over a range of 200-500 MPa at ambient temperature for dwell times ranging from 5 to 20 min. The physicochemical properties of jackfruit bulbs such as the pH, TSS, and titrable acidity were not affected by the pressurization process. The ripening index of the fruit bulb also decreased following HP treatment. While the ascorbic acid and antioxidant activity of jackfruit bulb were well retained by high pressure processing (HPP), the total phenols and carotenoids showed a slight increase. The HPP significantly affected the colour and textural properties of jackfruit bulb. High pressure processing was highly effective in reducing the browning index of jackfruit bulbs in comparison to untreated bulbs. The firmness of the bulbs improved upon the pressure treatment with longer dwelling time. The polyphenol oxidase has been identified as the most prominent oxidative enzyme in the jackfruit bulb. The enzymatic activity of polyphenol oxidase and peroxidase were significantly reduced by up to 40% following treatment at 400 MPa/15 min. HPP of jackfruit bulbs at ambient temperatures is shown to be highly beneficial in improving the shelf stability, retaining its nutrient profile, color, and appearance while ensuring the maximum inactivation of the spoilage enzymes.

Keywords: antioxidant capacity, ascorbic acid, carotenoids, color, HPP-high pressure processing, jackfruit bulbs, polyphenol oxidase, peroxidase, total phenolic content

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Authors: Ashit Syngle, Inderjit Verma, Pawan Krishan

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Therapeutic approaches used previously relied on disease-modifying antirheumatic drugs (DMARDs) that had only partial clinical benefit and were associated with significant toxicity. Spironolactone, an oral aldosterone antagonist, suppresses inflammatory mediators. Clinical efficacy of spironolactone compared with placebo in patients with active psoriatic arthritis despite treatment with prior traditional DMARDs. In the 24-week, placebo-controlled study patients (n=31) were randomized to placebo and spironolactone (2 m/kg/day). Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide, and/or sulfasalazine). Primary outcome measures were the assessment of disease activity measures i.e. 28-joint disease activity score (DAS28) and diseases activity in psoriatic arthritis (DAPSA) at week 24. The key secondary endpoint was change from baseline in Health Assessment Questionnaire–Disability Index (HAQ-DI) at week 24. Additional efficacy outcome measures at week 24 included improvements in the markers of inflammation (ESR and CRP) and pro-inflammatory cytokines TNF-α, IL-6 and IL-1. At week 24, spironolactone significantly reduced disease activity measure DAS-28 (p<0.001) and DAPSA (p=0.001) compared with placebo. Significant improvements in key secondary measures HAQ-DI (disability index) were evident with spironolactone (p=0.02) versus placebo. After week 24, there was significant reduction in pro-inflammatory cytokines level TNF-α, IL-6 (p<0.01) as compared with placebo group. However, there was no significant improvement in IL-1 in both treatment and placebo groups. There were minor side effects which did not mandate stopping of spironolactone. No change in any biochemical profile was noted after spironolactone treatment. Spironolactone was effective in the treatment of PsA, improving disease activity, physical function and suppressing the level of pro-inflammatory cytokines. Spironolactone demonstrated an acceptable safety profile and was well tolerated.

Keywords: spironolactone, inflammation, inflammatory cytokine, psoriatic arthritis

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Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu

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Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.

Keywords: tenofovir nanoparticles, liver, kidney, blood cells

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Authors: Parimalakrishnan Sundararjan, Madheswaran Murugan, Dhanya Dharman, Yatindra Kumar, Sudhir Singh Gangwar, Guru Prasad Mohanta

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Antibiotic resistance AR is a global issue, India started to redress the issues of antibiotic resistance late and it plans to have: active surveillance of microbial resistance and promote appropriate use of antibiotics. The present study attempted to achieve appropriate use of antibiotics through pharmacists’ intervention at practice point. In a quasi-experimental prospective cohort study, the cases with bacteremia from four hospitals were identified during 2015 and 2016 for intervention. The pharmacists centered intervention: active screening of each prescription and comparing with the selection of antibiotics with susceptibility of the bacteria. Wherever irrationality noticed, it was brought to the notice of the treating physician for making changes. There were two groups: intervention group and control group without intervention. The active screening and intervention in 915 patients has reduced therapeutic regimen time in patients with bacteremia. The intervention group showed the decreased duration of hospital stay 3.4 days from 5.1 days. Further, multivariate modeling of patients who were in control group showed that patients in the intervention group had a significant decrease in both duration of hospital stay and infection-related mortality. Unlike developed countries, pharmacists are not active partners in patient care in India. This unique attempt of pharmacist’ invention was planned in consultation with hospital authorities which proved beneficial in terms of reducing the duration of treatment, hospital stay, and infection-related mortality. This establishes the need for a collaborative decision making among the health workforce in patient care at least for promoting rational use of antibiotics, an attempt to combat resistance.

Keywords: antibiotics resistance, intervention, bacteremia, multivariate modeling

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Authors: Haris Karnezi, Kevin Tierney

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Cognitive Behaviour Drama is a research-based intervention model that brought together the science of psychology with the art form of drama to create an unobtrusive and exciting approach that would provide children on the higher end of the autism spectrum the motivation to explore the rules of social interaction and develop competencies associated with communicative success. The method involves engaging the participants in exciting fictional scenarios and encouraging them to seek various solutions on a number of problems that will lead them to an understanding of causal relationships and how a different course of action may lead to a different outcome. The sessions are structured to offer opportunities to the participants to practice target behaviours and understand the functions they serve. The study involved six separate interventions and employed both single case and group designs. Overall 8 children aged between 6 to 13 years, diagnosed with ASD participated in the study. Outcomes were measured using theory of mind tests, executive functioning tests, behavioural observations, pre and post intervention standardised social competence questionnaires for parents and teachers. Collectively, the results indicated positive changes in the self esteem and behaviour of all eight participants. In particular, improvements in the ability to solve theory of mind tasks were noted in the younger group; and qualitative improvements in social communication, in terms of verbal (content) and non verbal expression (body posture, vocal expression, fluency, eye contact, reduction of ritualistic mannerisms) were noted in the older group. The need for reliable impact measures to assess the effectiveness of the model in generating global changes in the participants’ behaviour outside the therapeutic context was identified.

Keywords: autism, drama, intervention, social skills

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Authors: Sahar Rakhshan, Simonetta Geninatti Crich, Diego Alberti, Rachele Stefania

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The combination of imaging and therapeutic agents in the same smart nanoparticle is a promising option to perform a minimally invasive imaging guided therapy. In this study, Low density lipoproteins (LDL), one of the most attractive biodegradable and biocompatible nanoparticles, were used for the simultaneous delivery of Paclitaxel (PTX), a hydrophobic antitumour drug and an amphiphilic contrast agent, Gd-AAZTA-C17, in B16-F10 melanoma cell line. These cells overexpress LDL receptors, as assessed by Flow cytometry analysis. PTX and Gd-AAZTA-C17 loaded LDLs (LDL-PTX-Gd) have been prepared, characterized and their stability was assessed under 72 h incubation at 37 ◦C and compared to LDL loaded with Gd-AAZTA-C17 (LDL-Gd) and LDL-PTX. The cytotoxic effect of LDL-PTX-Gd was evaluated by MTT assay. The anti-tumour drug loaded into LDLs showed a significantly higher toxicity on B16-F10 cells with respect to the commercially available formulation Paclitaxel Kabi (PTX Kabi) used in clinical applications. It was possible to demonstrate a high uptake of LDL-Gd in B16-F10 cells. As a consequence of the high cell uptake, melanoma cells showed significantly high cytotoxic effect when incubated in the presence of PTX (LDL-PTX-Gd). Furthermore, B16-F10 have been used to perform Magnetic Resonance Imaging. By the analysis of the image signal intensity, it was possible to extrapolate the amount of internalized PTX indirectly by the decrease of relaxation times caused by Gd, proportional to its concentration. Finally, the treatment with PTX loaded LDL on B16-F10 tumour bearing mice resulted in a marked reduction of tumour growth compared to the administration of PTX Kabi alone. In conclusion, LDLs are selectively taken-up by tumour cells and can be successfully exploited for the selective delivery of Paclitaxel and imaging agents.

Keywords: low density lipoprotein, melanoma cell lines, MRI, paclitaxel, personalized medicine application, theragnostic System

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Authors: D. Motlhanka, M. Mine, T. Bagaketse, T. Ngakane

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There is a plethora of evidence from numerous sources that highlights the triumph of naturally derived medicinal plant metabolites with antioxidant capability for repurposed therapeutics. As post-COVID-19 syndromes and non-communicable diseases are on the rise, there is an urgent need to come up with new therapeutic strategies to address the problem. Non-communicable diseases and Post COVID-19 syndromes are classified as socio-economic diseases and are ranked high among threats to health security due to the economic burden they pose to any government budget commitment. Research has shown a strong link between accumulation of free radicals and oxidative stress critical for pathogenesis of non-communicable diseases and COVID-19 syndromes. Botswana has embarked on a robust programme derived from ethno-pharmacognosy and drug repurposing to address these threats to health security. In the current approach, a number of medicinally active plant-derived polyphenolics are repurposed and combined into new medicinal tools to target diabetes, Hypertension, Prostate Cancer and oxidative stress induced Post COVID 19 syndromes such as “brain fog”. All four formulants demonstrated Free Radical scavenging capacities above 95% at 200µg/ml using the diphenylpicryalhydrazyl free radical scavenging assay and the total phenolic contents between 6899-15000GAE(g/L) using the folin-ciocalteau assay respectively. These repurposed medicinal tools offer new hope and potential in the fight against emerging health threats driven by hyper-inflammation and free radical-induced oxidative stress.

Keywords: drug repurposed plant polyphenolics, free radical damage, non-communicable diseases, post COVID 19 syndromes

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Authors: Dipali Dhawan

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Cancerous epithelial cells are confined to a primary site by the continued expression of adhesion molecules and the intact basal lamina. However, as the cancer progresses some cells are believed to undergo an epithelial-mesenchymal transition (EMT) event, leading to increased motility, invasion and, ultimately, metastasis of the cells from the primary tumour to secondary sites within the body. These disseminated cancer cells need the ability to self-renew, as stem cells do, in order to establish and maintain a heterogeneous metastatic tumour mass. Identification of the specific subpopulation of cancer stem cells amenable to the process of metastasis is highly desirable. In this study, we have isolated and characterized cancer stem cells from luminal and basal breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, MCF7 and T47D) on the basis of cell surface markers CD44 and CD24; as well as Side Populations (SP) using Hoechst 33342 dye efflux. The isolated populations were analysed for epithelial and mesenchymal markers like E-cadherin, N-cadherin, Sfrp1 and Vimentin by Western blotting and Immunocytochemistry. MDA-MB-231 cell lines contain a major population of CD44+CD24- cells whereas MCF7, T47D and MDA-MB-231 cell lines show a side population. We observed higher expression of N-cadherin in MCF-7 SP cells as compared to MCF-7NSP (Non-side population) cells suggesting that the SP cells are mesenchymal like cells and hence express increased N-cadherin with stem cell-like properties. There was an expression of Sfrp1 in the MCF7- NSP cells as compared to no expression in MCF7-SP cells, which suggests that the Wnt pathway is expressed in the MCF7-SP cells. The mesenchymal marker Vimentin was expressed only in MDA-MB-231 cells. Hence, understanding the breast cancer heterogeneity would enable a better understanding of the disease progression and therapeutic targeting.

Keywords: cancer stem cells, epithelial to mesenchymal transition, biomarkers, breast cancer

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Authors: Jenyu Peng

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Incestuous abuse can be considered a form of domestic violence that exemplifies gender inequality. It challenges the common image of home as “haven of safety”. In Taiwan, even after years of feminist NGOs’ effort to encourage victims to speak up, the shared cultural representations of family, still praising piety towards the parents, seem to keep the incest trauma in secret. As clinical practitioners have observed, most devastating psychological sequels of incest trauma are often related to silencing. Thus one can expect that in families centered cultures, the difficulties for victims to disclose are greater, and the traumatic consequences more severe. This poses crucial therapeutic issues for clinicians working in those cultures. Since 2009, the author, a trained psychoanalyst and researcher, has been conducting “clinical fieldwork” on incest trauma in Taiwan. Employing ethnographical method, our theoretical references are both psychoanalytical and anthropological. The necessity of interdisciplinary efforts in incest trauma research will be addressed and discussed. The analyses of the present paper will focus on five incestuous families: four Han families, and one aboriginal. Although Taiwanese aboriginal peoples have been pretty much sinicized since decades, it is worth observing the convergent and divergent aspects in these two cultures. Moreover, findings of a previous research conducted in France during 2002-2004 will serve as background for the purpose of comparison. The results will be presented along with three questions: 1) How the perception of family influences the process of disclosure? 2) How the incestuous experience comes into play with victims’ gender identity and sexuality, pivotal for the subjectification? 3) How victims more successful in gendered subjectification modify their dynamics with their traumatizing family? This research finds that most victims tend to defend their own incestuous families, and that victims’ subjectivity and agency are actually entangled in the power structure of incestuous family.

Keywords: incestuous family, subjectification, gender identity, agency

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Authors: Ghada Esheba, Ghadeer Aldoobi, Salwa Almalk, Abrar Alshareef, Eman Al-khairi, Eman Yaseen

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Background: In Saudi Arabia, ovarian cancer ranked seventh among female population and is the most common female genital tract malignancy after endometrial cancer. A slight increase in the incidence of ovarian cancer was observed from 2001–2008. Makkah, Riyadh, and the eastern region of Saudi Arabia had the highest incidence rate ratio for the number of ovarian cancer cases (1). Differentiating metastatic adenocarcinomas from primary ovarian carcinomas, especially those of endometrioid and mucinous type is clinically significant and a challenge for clinicians and pathologists, yet the distinction has important therapeutic and prognostic implications. Aim: To clarify the most important histopathological criteria to differentiate between primary ovarian surface epithelial tumors especially mucinous and endometrioid subtypes, and metastatic adenocarcinoma and to evaluate the value of a panel of antibodies consisting of CK7, CK20, and CDX-2 in the distinction between primary ovarian surface epithelial tumors and metastatic adenocarcinoma. Material and methods: This study was carried out on 26 cases of primary ovarian surface epithelial neoplasms and 14 cases of metastatic ovarian adenocarcinoma. All cases were studied immunohistochemically using CK7, CK20, and CDX-2. Results: All cases of primary ovarian adenocarcinoma were positive for CK7. 25% and 58% of mucinous borderline mucinous tumor and mucinous carcinoma respectively were positive for CK20. Only 42% of mucinous carcinoma were positive for CDX-2. All cases of endometrioid carcinomas were negative for both CK20 and CDX-2. All cases of metastatic adenocarcinoma from the colon were negative for CK7 and positive for CK20 and CDX-2. Conclusions: CK7 is an important positive marker for primary ovarian tumors, while CK20 and CDX-2 are useful markers for colorectal carcinoma metastatic to the ovary. Caution should be taken as primary ovarian mucinous tumors may stain positive for CK20, CDX-2, or both, however, they usually exhibit a focal pattern of reactivity.

Keywords: adenoma, endometrioid, malignancy, ovarian

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Authors: Manju Kanu, Subrata Sinha, Surabhi Johari

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Viral proteins of Ebola viruses belong to one of the best studied viruses; however no effective prevention against EBOV has been developed. Epitope-based vaccines provide a new strategy for prophylactic and therapeutic application of pathogen-specific immunity. A critical requirement of this strategy is the identification and selection of T-cell epitopes that act as vaccine targets. This study describes current methodologies for the selection process, with Ebola virus as a model system. Hence great challenge in the field of ebola virus research is to design universal vaccine. A combination of publicly available bioinformatics algorithms and computational tools are used to screen and select antigen sequences as potential T-cell epitopes of supertypes Human Leukocyte Antigen (HLA) alleles. MUSCLE and MOTIF tools were used to find out most conserved peptide sequences of viral proteins. Immunoinformatics tools were used for prediction of immunogenic peptides of viral proteins in zaire strains of Ebola virus. Putative epitopes for viral proteins (VP) were predicted from conserved peptide sequences of VP. Three tools NetCTL 1.2, BIMAS and Syfpeithi were used to predict the Class I putative epitopes while three tools, ProPred, IEDB-SMM-align and NetMHCII 2.2 were used to predict the Class II putative epitopes. B cell epitopes were predicted by BCPREDS 1.0. Immunogenic peptides were identified and selected manually by putative epitopes predicted from online tools individually for both MHC classes. Finally sequences of predicted peptides for both MHC classes were looked for common region which was selected as common immunogenic peptide. The immunogenic peptides were found for viral proteins of Ebola virus: epitopes FLESGAVKY, SSLAKHGEY. These predicted peptides could be promising candidates to be used as target for vaccine design.

Keywords: epitope, b cell, immunogenicity, ebola

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Authors: Atif Zafar Khan, Swarnendra Singh, Imrana Naseem

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Breast cancer is one of the most frequent malignancies in women worldwide and a leading cause of cancer-related deaths among women. Therefore, there is a need to identify new chemotherapeutic strategies for cancer treatment. Unlike normal cells, cancer cells contain elevated copper levels which play an integral role in angiogenesis. Copper is an important metal ion associated with the chromatin DNA, particularly with guanine. Thus, targeting copper via copper-specific chelators in cancer cells can serve as effective anticancer strategy. Keeping in view these facts, we evaluated the anticancer activity and copper-dependent cytotoxic effect of coumestrol (phytoestrogen in soybean products) in breast cancer MCF-7 cells. Coumestrol inhibited proliferation and induced apoptosis in MCF-7 cells, which was prevented by copper chelator neocuproine and ROS scavengers. Coumestrol treatment induced ROS generation coupled to DNA fragmentation, up-regulation of p53/p21, cell cycle arrest at G1/S phase, mitochondrial membrane depolarization and caspases 9/3 activation. All these effects were suppressed by ROS scavengers and neocuproine. These results suggest that coumestrol targets elevated copper for redox cycling to generate ROS leading to DNA fragmentation. DNA damage leads to p53 up-regulation which directs the cell cycle arrest at G1/S phase and promotes caspase-dependent apoptosis of MCF-7 cells. In conclusion, coumestrol induces pro-oxidant cell death by chelating cellular copper to produce copper-coumestrol complexes that engages in redox cycling in breast cancer cells. Thus, targeting elevated copper levels might be a potential therapeutic strategy for selective cytotoxic action against malignant cells.

Keywords: apoptosis, breast cancer, copper chelation, coumestrol, reactive oxygens species, redox cycling

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Authors: Manal Ahmed, Amal Shehata, Shereen Deeb

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The study's purpose was to determine the effect of the perioperative protocol of care on clinical outcomes among patients undergoing coronary artery bypass graft. Subjects: A sample of 100 adult patients who were planned for coronary artery bypass graft, were selected and divided alternatively and randomly into two equal groups (50 study -50 control).The study was carried out at National heart Institute in Cairo and open heart surgical intensive care unit in Shebin El-Kom Teaching Hospital. Instruments: Four instruments were used for data collection: Interviewing questionnaire, dyspnea analogue scale, Biophysiological measurement instrument, and Compliance assessment sheet. Results: There were statistically significant differences between both groups regarding most respiratory system assessment findings at discharge. More than two-thirds of the study group of the current study had a continuous and regular commitment to diet regimen, which ranked first followed by the compliance of daily living activities then quitting smoking. Conclusions: The perioperative protocol of care has a significant improving effect on respiratory findings, dyspnea degree, duration of mechanical ventilation, length of hospital stay, compliance to diet, therapeutic regimen, daily living activities, and quit smoking among study group undergoing CABG. Recommendations: Perioperative protocol of care should be carried out for CABG patients at open-heart surgical units as well as an illustrative colored booklet about CAD, CABG and perioperative care should be available and distributed to all CABG patients.

Keywords: perioperative, effect, clinical outcomes, coronary artery, bypass graft, protocol of care

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Authors: Jawaher F. Alsharef, Abdullah A. Ghaddaf, Mohammed S. Alomari, Abdullah A. Al Qurashi, Ahmed S. Abdulhamid, Mohammed S. Alshehri, Majed Alosaimi

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Botulinum toxin type A (BTX-A) is the most popular therapeutic agent for muscle relaxation and pain control. Lately, BTX-A injection received great interest as a part of multimodal pain management for lower limb lengthening and deformity correction. This systematic review aimed to determine the role of BTX-A injection in pain management for during lower limb lengthening and/or deformity correction. We searched Medline, Embase, and CENTRAL. We included randomized controlled trials (RCTs) that compared the BTX-A injection to placebo for individuals undergoing lower limb lengthening and/or deformity correction. We sought to evaluate the following outcomes: pain on visual analogue scale (VAS), range of motion parameters, average opioid consumption, and adverse events. The standardized mean difference (SMD) was used to represent continuous outcomes while risk ratio (RR) was used to represent dichotomous outcomes. A total of 4 RCTs that enrolled 257 participants (337 limbs) deemed eligible. Adjuvant BTX-A injection showed a significant reduction in post-operative pain compared to placebo (SMD=–0.28, 95% CI –0.53 to –0.04). No difference was found between BTX-A injection and placebo in terms of range of motion parameters, average opioid consumption, or adverse events after surgical limb lengthening and/or deformity correction (RR= 0.77, 95% CI –0.58 to 1.03). Conclusions: Adjuvant BTX-A injection conferred a discernible reduction in post-operative pain during surgical limb lengthening and/or deformity without increasing the risk of adverse events.

Keywords: botulinum toxin type A, limb lengthening, distraction osteogenesis, deformity correction, pain management

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Authors: Daniele Zullino, Gabriel Thorens, Léonice Furtado, Federico Seragnoli, Radu Iuga, Louise Penzenstadler

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Context: Since the start of the 21st century, there has been a resurgence of interest in psychedelics, marked by a renewed focus on scientific investigations into their therapeutic potential. While psychedelic therapy has gained recognition for effectively treating depression and anxiety disorders, notable progress has been made in the clinical development of substances like psilocybin. Moreover, mounting evidence suggests promising applications of Lysergic acid diethylamide (LSD) and psilocybin in the field of addiction medicine. In Switzerland, compassionate treatment with LSD and psilocybin has been permitted since 2014 through exceptional licenses granted by the Federal Office of Public Health. This treatment approach is also available within the Geneva treatment program, extending its accessibility to patients undergoing opioid-assisted treatment involving substances like morphine and diacetylmorphine. The aim of this study is to assess the feasibility of psychedelic-assisted therapy in patients with opioid use disorder who are undergoing opioid-assisted treatment. This study addresses the question of whether psychedelic-assisted therapy can be successfully implemented in patients with opioid use disorder. It also explores the effects of psychedelic therapy on the patient's experiences and outcomes. Methodology: This is an open case series on six patients who have undergone at least one session with either LSD (100-200 micrograms) or psilocybin (20-40 mg). The patients were assessed using the Five Dimensional Altered States of Consciousness (5D-ASC)-Scale. The data were analyzed descriptively to identify patterns and trends in the patients' experiences. Results: The patients experienced substantial positive psychedelic effects during the psychedelic sessions without significant adverse effects. The patients reported positive experiences and improvements in their condition. Conclusion: The findings of this study support the feasibility and potential efficacy of psychedelic-assisted therapy in patients undergoing opioid-assisted treatment.

Keywords: psychedelics, psychedelic-assisted treatment, opioid use disorder, addiction, LSD, psilocybin

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Authors: Ali Kassem

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Background: In the last few years, factors such as insulin resistance (IR) and hepatic steatosis have been linked to progression of hepatic fibrosis.Patients with chronic liver disease, and cirrhosis in particular, are known to be prone to IR. However, chronic HCV (hepatitis C) infection may induce IR, regardless of the presence of liver cirrhosis. Our aims are to study insulin resistance (IR) assessed by HOMA-IR (Homeostatic Model Assessment Insulin Resistance) as a possible risk factor in disease progression in cirrhotic patients and to evaluate the role of IR in hepatic fibrosis progression. The correlations of HOMA-IR values to laboratory, virological and histopathological parameters of chronic HCV are also examined. Methods: The study included 50 people divided into 30 adult chronic hepatitis C patients diagnosed by PCR (polymerase chain reaction) within previous 6 months and 20 healthy controls. The functional and morphological status of the liver were evaluated by ultrasonography and laboratory investigations including liver function tests and by liver biopsy. Fasting blood glucose and fasting insulin levels were measured and body mass index and insulin resistance were calculated. Patients having HOMA-IR >2.5 were labeled as insulin resistant. Results: Chronic hepatitis C patients with IR showed significantly higher mean values of BMI (body mass index) and fasting insulin than those without IR (P < 0.000). Patients with IR were more likely to have steatosis (p = 0.006), higher necroinflammatory activity (p = 0.05). No significant differences were found between the two groups regarding hepatic fibrosis. Conclusion: HOMA-IR measurement could represent a novel marker to identify the cirrhotic patients at greater risk for the progression of liver disease. As IR is a potentially modifiable risk factor, these findings may have important prognostic and therapeutic implications. Assessment of IR by HOMA-IR and improving insulin sensitivity are recommended in patients with HCV and related chronic liver disease.

Keywords: hepatic fibrosis, hepatitis C virus infection, hepatic steatosis, insulin resistance

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Authors: Shirajul Islam Khan, Muhammad Ashraful Alam Bhuiyan, Syeda Tania Begum

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Introduction: Acne vulgaris is one of the most common dermatologic conditions and affects the vast majority of people at some point during their lifetime, so effective treatment is of major importance. The failure of usual treatment modalities, teratogenic effects with some severe side effects, and resistance to P.Acne by Retinoides have been focusing on new therapeutic options for the treatment of acne. More recently, pulsed dye laser therapy has been reported to reduce acne lesion counts. The negligible morbidity of these treatment modalities and some other benefits of subsequent acne scar management lead this therapy more attractive. Objective: The objective of this study is to assess the efficacy and safety of pulsed dye laser therapy in the treatment of inflammatory acne vulgaris. Materials and Methods: A prospective clinical trial was done in the Department of Dermatology and Venereology, Combined Military Hospital (CMH), Dhaka, to find out the role of pulse dye laser in the treatment of inflammatory acne vulgaris. The study was carried out with 60 patients with mild to moderate acne vulgaris, and those were treated with pulsed dye laser therapy at baseline and after 4, 8, and 12 weeks. Results: Among 60 patients with inflammatory acne, 42(70%) were in the age group of less than 20 years, and 36(60%) were female. Regarding the number of inflammatory lesions, the baseline mean number (± SD) was 12.77 ± 4.01; after 4 weeks of treatment of inflammatory acne by pulsed dye laser was 7.80 ± 4.11; after 8 weeks of treatment, 6.10 ± 4.03 and after 12 weeks of treatment was 4.17 ± 4.02. After 4 weeks of treatment by pulse dye laser, the level of improvement was excellent at 3.3%, good at 10%, fair at 60%, and poor at 26.7%; after 8 weeks of treatment, excellent was 13.3%, good was 46.7%, the fair was 30% and poor 10% and after 12 weeks of treatment, excellent was 56.7%, good 13.3%, fair 23.3% and poor 6.7%. Regarding safety level, out of 60 patients of inflammatory acne vulgaris treated by pulsed dye laser, about 52(86.7%) patients did not observe any side effects. Conclusions: On the basis of the study results, it can be concluded that pulsed-dye laser is highly effective and well tolerated by patients in the treatment of inflammatory acne.

Keywords: pulsed-dye laser, inflammatory acne, acne vulgaris, retinoids

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Authors: M. Marjaneh, M. Y. Narazah, H. Shahrul

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Array-based gene expression analysis is a powerful tool to profile expression of genes and to generate information on therapeutic effects of new anti-cancer compounds. Anti-apoptotic effect of thymoquinone was studied in MCF7 breast cancer cell line using gene expression profiling with cDNA micro array. The purity and yield of RNA samples were determined using RNeasyPlus Mini kit. The Agilent RNA 6000 Nano LabChip kit evaluated the quantity of the RNA samples. AffinityScript RT oligo-dT promoter primer was used to generate cDNA strands. T7 RNA polymerase was used to convert cDNA to cRNA. The cRNA samples and human universal reference RNA were labelled with Cy-3-CTP and Cy-5-CTP, respectively. Feature Extraction and GeneSpring software analysed the data. The single experiment analysis revealed involvement of 64 pathways with up-regulated genes and 78 pathways with down-regulated genes. The MAPK and p38-MAPK pathways were inhibited due to the up-regulation of PTPRR gene. The inhibition of p38-MAPK suggested up-regulation of TGF-ß pathway. Inhibition of p38 - MAPK caused up-regulation of TP53 and down-regulation of Bcl2 genes indicating involvement of intrinsic apoptotic pathway. Down-regulation of CARD16 gene as an adaptor molecule regulated CASP1 and suggested necrosis-like programmed cell death and involvement of caspase in apoptosis. Furthermore, down-regulation of GPCR, EGF-EGFR signalling pathways suggested reduction of ER. Involvement of AhR pathway which control cytochrome P450 and glucuronidation pathways showed metabolism of Thymoquinone. The findings showed differential expression of several genes in apoptosis pathways with thymoquinone treatment in estrogen receptor-positive breast cancer cells.

Keywords: cDNA microarray, thymoquinone, CARD16, PTPRR, CASP10

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Authors: Ndarusanze Berchmans

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This research work focused on the analysis of the observations of tuberculous meningitis in HIV-positive patients who were treated by the Prince Regent Charles Hospital in Bujumbura. A number of 246 seropositive patients were examined by the laboratory of Prince Regent Charles in the period between 2010 and 2015. We did a retrospective study; we used data from the registers of the laboratories mentioned above; the objective was to approach the epidemiological, biological, clinical, and therapeutic characteristics of tuberculosis meningitis infection: 124 women (50.40% of AIDS patients) and 122 men (49.59% of AIDS patients) were subject to the diagnosis by identification of cerebrospinal fluid (CSF). The average age of the patients was 30 years for this period. The population at risk has an average age of between 34 and 42 years for the years between 2010-2015. From 2010 to 2012, cases of opportunistic diseases (e.g., tuberculous meningitis and Cryptococcus neoformans meningitis), often found in immunocompromised, were observed at a high rate; in this period, there was a disturbance of the rhythm providing antiretroviral drugs to people with AIDS. The rate of the two meningitis (tuberculous meningitis and Cryptococcus neoformans meningitis) remained above 10% to gradually decrease until 2015, with the gradual return of antiretrovirals. This period records an overall average of 25 cases of tuberculous meningitis, or a percentage of 10.16%. For the year 2015, there were 4 cases of tuberculous meningitis out of a total of 35 seropositive examined (11.42%). This year's percentage shows that the number of tuberculous meningitis cases has fallen from the rate in previous years. This is the result of the care given by associations against HIV/AIDS to HIV-positive people. This decrease in cases of tuberculous meningitis is due to the acquisition of antiretrovirals by all HIV-positive people treated by hospitals. For the moment, these hospitals are taking care of many AIDS patients by providing them permanently with antiretrovirals; Besides that, there are many patients who are supported by associations whose activities are directed against HIV/AIDS.

Keywords: Cryptococcus neoformans meningitis, tuberculosis meningitis, neurological complications, epidemiology of meningitis

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Authors: Tahira Hyder, Saima Quraeshi, Zohaib Akram

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Salvadora Persica (SP) is known to have anti-inflammatory, antioxidant, anti-coagulant and anti-bacterial properties that may provide therapeutic benefits in the treatment of chronic periodontitis (CP). The current clinical trial was designed to investigate the clinical and anti-microbial effects of SP gel as an adjunct to scaling and root planning (SRP) in subjects with generalized CP. Sixty-six subjects with CP were randomized allocated into two groups: SRP + SP gel (test group) and SRP only (control group). Clinical parameters (periodontal pocket depth, gingival recession, clinical attachment level, bleeding score and plaque score) were recorded at baseline before SRP and at 6 weeks. At baseline and 6 weeks subgingival plaque samples were collected and periodontopathogen Porphyromonas Gingivalis (Pg) quantified using Real-time Polymerase Chain Reaction (RT-PCR). Both therapies reduced the mean periodontal pocket depth (PPD), plaque score (PS) and bleeding score (BOP) and improved the mean clinical attachment level (CAL) between baseline and 6 weeks. In subjects receiving adjunctive SP gel a statistically significant improvement was observed in BOP at follow-up compared to control group (15.01±3.47% and 22.81±6.81% respectively, p=0.001), while there was no statistically significant difference in periodontal pocket depth, gingival recession, clinical attachment level and plaque score between both groups. The test group displayed significantly greater Pg reduction compared to the control group after 6 weeks. The current study establishes that local delivery of SP gel into periodontal pocket in CP stimulated a significant reduction in bacteria Pg level and an improvement in gingival health, as evident from a reduced bleeding score, when used as an adjunct to SRP.

Keywords: miswak, scaling and root planing, porphyromonas gingivalis, chronic periodontitis

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Authors: Fleura Shkëmbi, Valbona Treska

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In elementary school, we discover that a metaphor is a decorative linguistic device just for poets. But now that we know, it's also a crucial tactic that individuals employ to understand the universe, from fundamental ideas like time and causation to the most pressing societal challenges today. Metaphor is the use of language to refer to something other than what it was originally intended for or what it "literally" means in order to suggest a similarity or establish a connection between the two. People do not identify metaphors as relevant in their decisions, according to a study on metaphor and its effect on decision-making; instead, they refer to more "substantive" (typically numerical) facts as the basis for their problem-solving decision. Every day, metaphors saturate our lives via language, cognition, and action. They argue that our conceptions shape our views and interactions with others and that concepts define our reality. Metaphor is thus a highly helpful tool for both describing our experiences to others and forming notions for ourselves. In therapeutic contexts, their shared goal appears to be twofold. The cognitivist approach to metaphor regards it as one of the fundamental foundations of human communication. The benefits and disadvantages of utilizing the metaphor differ depending on the target domain that the metaphor portrays. The challenge of creating messages and surroundings that affect customers' notions of abstract ideas in a variety of industries, including health, hospitality, romance, and money, has been studied for decades in marketing and consumer psychology. The aim of this study is to examine, through a systematic literature review, the role of the metaphor in communication and in advertising. This study offers a selected analysis of this literature, concentrating on research on customer attitudes and product appraisal. The analysis of the data identifies potential research questions. With theoretical and applied implications for marketing, design, and persuasion, this study sheds light on how, when, and for whom metaphoric communications are powerful.

Keywords: metaphor, communication, advertising, cognition, action

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Authors: Rawan Al-Nemari, Abdulrahman Al-Senaidy, Abdelhabib Semlali

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Background and objectives: The most common cause of death in women worldwide is breast cancer. Regarding all chemotherapy disadvantages and side effects, it’s becoming necessary to identify natural products that target cancer cells with lesser harmful side effects on non-targeted cells and biological environment. Different parts of A. squamosa L., commonly known as custard apple, show varied therapeutic effects. The objective of this study is to investigate in vitro and in vivo, the anti-cancer activity of A. squamosa leaves extract. Methods: The physiological responses using MTT, nucleus staining, and LDH assays were used to evaluate cell survival and proliferation in both ER+ and ER- cells when they were exposed to extract. Monolayer wound repair assay was used to investigate the effect of extracts on cell migration. Apoptotic gene’s expression was investigated by real-time polymerase chain reaction. To study the effect of the extract on the size of tumor, breast cancer induced rats were used. Results: A. squamosa leaves extract showed high anti-proliferative and cytotoxicity effects against different breast cancer cell lines with high concentration, 100 ug/ml. The extracts have reduced the cells wound closure. Polymerase chain reaction revealed downregulation of Bcl-2 and upregulation of Bax. In breast cancer model animal developed in our laboratory, after 4 weeks treatment, treated groups have shown smaller tumor size in comparison with control group (n=4). Conclusion: These results suggest that A. squamosa leaves extract has anti-cancer activity against breast cancer in both in vitro and in vivo, and it may be developed as a potential novel agent to treat breast cancer.

Keywords: apoptosis, breast cancer, migration, proliferation

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Authors: Svitlana Antonenko, Gennady Telegeev

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Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

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Authors: Leila Asadollahi

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Dry powder inhalers (DPIs) have come a long way since their creation, starting with the Spinhaler Fisons in 1967. For optimal performance, it is important to consider the interplay between formulation, device, and patient. DPIs have shown great potential in treating systemic disorders, as evidenced by their success in clinical practices. Ongoing clinical trials and market availability of DPI products for systemic disease treatment are also examined. Furthermore, the current COVID-19 pandemic has sparked increased interest in dry powder inhalation as a potential avenue for vaccines and antiviral drugs, prompting further exploration of its applications. To achieve optimal treatment outcomes for respiratory diseases, a thorough understanding of the various types of DPIs currently available is crucial. These include single-dose, multiple-unit dose, and multi-dose DPIs. This informative article delves into the administration of drugs via inhalation, examining its diverse routes of administration. Additionally, it illuminates the exciting advancements in inhalation delivery systems and investigates the latest therapeutic approaches for the treatment of respiratory ailments. Additionally, the article discusses the historical development of DPIs and the need for improved designs to enhance efficacy and patient adherence. The potential of DPIs in treating systemic diseases is also examined. Overall, this review provides valuable insights into the advancements, challenges, and future prospects of inhalation drug delivery systems, highlighting the potential they hold for respiratory and systemic disorders. The review aims to provide valuable insights into the advancements, challenges, and future prospects of inhalation drug delivery systems, highlighting the potential they hold for respiratory and systemic disorders.

Keywords: dry powder inhalers (DPIs), respiratory diseases, systemic disorders, pulmonary drug delivery

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