Search results for: therapeutic agents

Authors: Fisaha Asmelash

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The processing of textiles to achieve a desired handle is a crucial aspect of finishing technology. Softeners can enhance the properties of textiles, such as softness, smoothness, elasticity, hydrophilicity, antistatic properties, and soil release properties, depending on the chemical nature used. However, human skin is sensitive to rough textiles, making softeners increasingly important. Although synthetic softeners are available, they are often expensive and can cause allergic reactions on human skin. This paper aims to extract a natural softener from Ricinus communis and produce an eco-friendly and user-friendly alternative due to its 100% herbal and organic nature. Crushed Ricinus communis seeds were soaked in a mechanical oil extractor for one hour with a 100g cotton fabric sample. The defatted cake or residue obtained after the extraction of oil from the seeds, also known as Ricinus communis meal, was obtained by filtering the raffinate and then dried at 1030c for four hours before being stored under laboratory conditions for the softening process. The softener was applied directly to 100% cotton fabric using the padding process, and the fabric was tested for stiffness, crease recovery, and drape ability. The effect of different concentrations of finishing agents on fabric stiffness, crease recovery, and drape ability was also analyzed. The results showed that the change in fabric softness depends on the concentration of the finish used. As the concentration of the finish was increased, there was a decrease in bending length and drape coefficient. Fabrics with a high concentration of softener showed a maximum decrease in drape coefficient and stiffness, comparable to commercial softeners such as silicon. The highest decrease in drape coefficient was found to be comparable with commercial softeners, silicon. Maximum increases in crease recovery were seen in fabrics treated with Ricinus communis softener at a concentration of 30gpl. From the results, the extracted softener proved to be effective in the treatment of 100% cotton fabric

Keywords: ricinus communis, crease recovery, drapability, softeners, stiffness

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Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

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Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

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Authors: Sheriff Muhammad Ibrahim

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The contemporary world has seen many agents of market liberalization, globalization, and expansion in agribusiness, which pose a big threat to the existence of smallholder farmers in the farming business or, at most, being marginalized against government interventions, investors' partnerships and further stretched by government policies in an effort to promote subsistent farming that can generate profits and speedy growth through attracting foreign businesses. The consequence of these modern shifts ends basically at the expense of smallholder farmers. Many scholars believed that this shift was among the major causes of urban-rural drift facing almost all communities in the World. In an effort to address these glaring economic crises, various governments at different levels and development agencies have created different programs trying to identify other sources of income generation for rural farmers. However, despite the different approaches adopted by many communities and states, the mass rural exodus continues to increase as the rural farmers continue to lose due to a lack of reliable sources for cost-efficient inputs such as agricultural extension services, mechanization supports, quality, and improved seeds, soil matching fertilizers and access to credit facilities and profitable markets for rural farmers output. Unfortunately for them, they see these agricultural requirements provided by large-scale farmers making their farming activities cheaper and yields higher. These have further created other social problems between the smallholder farmers and the large-scale farmers in many areas. This study aims to suggest the Islamic mode of agricultural financing named Muzara’ah for smallholder farmers as a microfinance banking product adopted and practiced by Yobe Microfinance Bank as a model to promote agricultural financing to be adopted in other communities. The study adopts a comparative research method to conclude that the Muzara’ah model of financing can be adopted as a valid means of financing smallholder farmers and reducing food insecurity.

Keywords: Muzara'ah, Islamic finance, agricultural financing, microfinance, smallholder farmers

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Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino

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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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Authors: Sabina Klimek

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In general, entrepreneurs are viewed as agents of change whose goal is to ensure that resources are efficiently utilized. They are very important in the global economy; they create wealth and provide jobs. At the same time, many policymakers say that women entrepreneurs are a ‘special group’ worthy of their own research and policies. The status of Polish women has been changing as well, even though, to a large extent, it is still defined by the double role that women are expected to fill according to the dominant stereotypical model of family life. However, in the past decade, Polish women’s economic activities have experienced rapid growth and today are at a high level. In the article, the author presents the results of a survey conducted among women entrepreneurs in Poland concerning the functioning of their enterprises, motivation in setting up a company, and barriers that hinder them in business. The questionnaire (300 questionnaires were provided) and case studies carried out by the author have proven that female entrepreneurs in Poland are characterized by commonalities. Mostly they run small or micro-enterprises, operate in larger cities, are well-educated, and run service companies. Their main motivation to run their own business is mostly indicated by their need for independence. However, one of their biggest barriers and hesitations is the apprehension of non-payment. Entrepreneurs want to develop their companies, go to foreign markets and implement new solutions. They are not afraid of the future; they are only trying to create it. Detailed hypothesis, which reads as follows. The author additionally conducted a macroeconomic analysis calculating what part of GDP in Poland is produced by female entrepreneurs. The results of the study presented in this article prove that female entrepreneurship in Poland has a stable impact on the economy of the country, and women entrepreneurs produce over 13% of the national GDP. After years of growth in the number of female entrepreneurs in Poland, there has been a period of stabilization. However, there has also been a reduction in the number of self-employed people as well as the number of women in total employment. In the article, the author analyses the reasons for decreasing number of self-employed women and the total employment of women in Poland and provides suggestions for steps and incentives that should be made in order to encourage female entrepreneurship to grow in the country.

Keywords: women entrepreneurship, women in business, women entrepreneurship in Poland, Poland, GDP of Poland

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Authors: Paulina Zavistanaviciute, Vita Krungleviciute, Elena Bartkiene

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Lactic acid bacteria (LAB) are microbial supplements that increase the nutritional, therapeutic, and safety value of food and feed. Often LAB strains are incubated in an expensive commercially available de Man-Rogosa-Sharpe (MRS) medium; the cultures are centrifuged, and the cells are washing with sterile water. Potato juice and apple juice industry bio-products are industrial wastes which may constitute a source of digestible nutrients for microorganisms. Due to their low cost and good chemical composition, potato juice and apple juice production bio- products could have a potential application in LAB encapsulation. In this study, pure LAB (P. acidilactici and P. pentosaceus) were multiplied in a crushed potato juice and apple juice industry bio-products medium. Before using, bio-products were sterilized and filtered. No additives were added to mass, except apple juice industry bioproducts were diluted with sterile water (1/5; v/v). The tap of sterilised mass, and LAB cell suspension (5 mL), containing of 8.9 log10 colony-forming units (cfu) per mL of the P. acidilactici and P. pentosaceus was used to multiply the LAB for 72 h. The final colony number in the potato juice and apple juice bio- products substrate was on average 9.60 log10 cfu/g. In order to stabilize the LAB, several methods of dehydration have been tested: lyophilisation (MilrockKieffer Lane, Kingston, USA) and dehydration in spray drying system (SD-06, Keison, Great Britain). Into the spray drying system multiplied LAB in a crushed potato juice and apple juice bio-products medium was injected in peristaltic way (inlet temperature +60 °C, inlet air temperature +150° C, outgoing air temperature +80 °C, air flow 200 m3/h). After lyophilisation (-48 °C) and spray drying (+150 °C) the viable cell concentration in the fermented potato juice powder was 9.18 ± 0.09 log10 cfu/g and 9.04 ± 0.07 log10 cfu/g, respectively, and in apple mass powder 8.03 ± 0.04 log10 cfu/g and 7.03 ± 0.03 log10 cfu/g, respectively. Results indicated that during the storage (after 12 months) at room temperature (22 +/- 2 ºC) LAB count in dehydrated products was 5.18 log10 cfu/g and 7.00 log10 cfu/g (in spray dried and lyophilized potato juice powder, respectively), and 3.05 log10 cfu/g and 4.10 log10 cfu/g (in spray dried and lyophilized apple juice industry bio-products powder, respectively). According to obtained results, potato juice could be used as alternative substrate for P. acidilactici and P. pentosaceus cultivation, and by drying received powders can be used in food/feed industry as the LAB starters. Therefore, apple juice industry by- products before spray drying and lyophilisation should be modified (i. e. by using different starches) in order to improve its encapsulation.

Keywords: bio-products, encapsulation, lactic acid bacteria, sustainability

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Authors: Alessandra Rossodivita, Alexei Tikhomirov, Andrey Trufanov, Nikolay Kinash, Olga Berestneva, Svetlana Nikitina, Fabio Casati, Alessandro Visconti, Tommaso Saporito

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It is well known that world and national societies are exposed to diverse threats: anthropogenic, technological, and natural. Anthropogenic ones are of greater risks and, thus, attract special interest to researchers within wide spectrum of disciplines in efforts to lower the pertinent risks. Some researchers showed by means of multilayered, complex network models how media promotes the prevention of disease spread. To go further, not only are mass-media sources included in scope the paper suggests but also personificated social bots (socbots) linked according to reflexive theory. The novel scope considers information spread over conscious and unconscious agents while counteracting both natural and man-made threats, i.e., infections and terrorist hazards. Contrary to numerous publications on misinformation disseminated by ‘bad’ bots within social networks, this study focuses on ‘good’ bots, which should be mobilized to counter the former ones. These social bots deployed mixture with real social actors that are engaged in concerted actions at spreading, receiving and analyzing information. All the contemporary complex network platforms (multiplexes, interdependent networks, combined stem networks et al.) are comprised to describe and test socbots activities within competing information sharing tools, namely mass-media hubs, social networks, messengers, and e-mail at all phases of disasters. The scope and concomitant techniques present evidence that embedding such socbots into information sharing process crucially change the network topology of actor interactions. The change might improve or impair robustness of social network environment: it depends on who and how controls the socbots. It is demonstrated that the topological approach elucidates techno-social processes within the field and outline the roadmap to a safer world.

Keywords: complex network platform, counterterrorism, information sharing topology, social bots

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Authors: Li Chun Zhao, Zhi Chao Hu, Xi Qiang Liu, Man Lai Lee, Chak Shing Yeung, Man Fei Xu, Yuen Yee Kwan, Alan H. M. Ho, Nickie W. K. Chan, Bin Deng, Zhong Zhen Zhao, Min Xu

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Background: Chuangxiong Rhizoma (Chuangxion, CX) is one of the most frequently used herbs in Chinese medicine because of its wide therapeutic effects such as vasorelaxation and anti-inflammation. Aim: The purposes of this study are (1) to perform non-targeted / targeted analyses of CX methanol extract and water extract, and compare the present data with previously LC-MS or GC-MS fingerprints; (2) to examine the difference between CX methanol extract and water extract for preliminarily evaluating whether current compound markers of methanol extract from crude CX materials could be suitable for quality control of CX water extract. Method: CX methanol extract was prepared according to the Hong Kong Chinese Materia Medica Standards. DG water extract was prepared by boiling with pure water for three times (one hour each). UHPLC-Q-TOF-MS/MS fingerprint analysis was performed by C18 column (1.7 µm, 2.1 × 100 mm) with Agilent 1290 Infinity system. Experimental data were analyzed by Agilent MassHunter Software. A database was established based on 13 published LC-MS and GC-MS CX fingerprint analyses. Total 18 targeted compounds in database were selected as markers to compare present data with previous data, and these markers also used to compare CX methanol extract and water extract. Result: (1) Non-targeted analysis indicated that there were 133 compounds identified in CX methanol extract, while 325 compounds in CX water extract that was more than double of CX methanol extract. (2) Targeted analysis further indicated that 9 in 18 targeted compounds were identified in CX methanol extract, while 12 in 18 targeted compounds in CX water extract that showed a lower lose-rate of water extract when compared with methanol extract. (3) By comparing CX methanol extract and water extract, Senkyunolide A (+1578%), Ferulic acid (+529%) and Senkyunolide H (+169%) were significantly higher in water extract when compared with methanol extract. (4) Other bioactive compounds such as Tetramethylpyrazine were only found in CX water extract. Conclusion: Many new compounds in both CX methanol and water extracts were found by using UHPLC Q-TOF MS/MS analysis when compared with previous published reports. A new standard reference including non-targeted compound profiling and targeted markers functioned especially for quality control of CX water extract (herbal decoction) should be established in future. (This project was supported by Hong Kong Baptist University (FRG2/14-15/109) & Natural Science Foundation of Guangdong Province (2014A030313414)).

Keywords: Chuanxiong rhizoma, fingerprint analysis, targeted analysis, quality control

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Authors: Dylan Santos De Pinho, Arnaud Gay De Combes, Matthieu Steuhlet, Claude Jeannerat, Nabil Ouerhani

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The Industry 4.0 initiative has been launched to address huge challenges related to ever-smaller batch sizes. The end-user need for highly customized products requires highly adaptive production systems in order to keep the same efficiency of shop floors. Most of the classical Software solutions that operate the manufacturing processes in a shop floor are based on rigid Manufacturing Execution Systems (MES), which are not capable to adapt the production order on the fly depending on changing demands and or conditions. In this paper, we present a highly modular and flexible solution to orchestrate a set of production systems composed of a micro-milling machine-tool, a polishing station, a cleaning station, a part inspection station, and a rough material store. The different stations are installed according to a novel matrix configuration of a 3x3 vertical shelf. The different cells of the shelf are connected through horizontal and vertical rails on which a set of shuttles circulate to transport the machined parts from a station to another. Our software solution for orchestrating the tasks of each station is based on a Multi-Agent System. Each station and each shuttle is operated by an autonomous agent. All agents communicate with a central agent that holds all the information about the manufacturing order. The core innovation of this paper lies in the path planning of the different shuttles with two major objectives: 1) reduce the waiting time of stations and thus reduce the cycle time of the entire part, and 2) reduce the disturbances like vibration generated by the shuttles, which highly impacts the manufacturing process and thus the quality of the final part. Simulation results show that the cycle time of the parts is reduced by up to 50% compared with MES operated linear production lines while the disturbance is systematically avoided for the critical stations like the milling machine-tool.

Keywords: multi-agent systems, micro-manufacturing, flexible manufacturing, transfer systems

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Authors: Sylvie Studente

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Despite the increase in international students migrating to the UK, the transition from home environment to a host institution abroad can be overwhelming for many students due to acculturative stressors. These stressors are reported to peak within the first six months of transitioning into study abroad which has determinantal impacts for Higher Education Institutions. These impacts include; increased drop-out rates and overall decreases in academic performance. Research suggests that belongingness can negate acculturative stressors through providing opportunities for students to form necessary social connections. In response to this universities have focussed on utilising technology to create learning communities with the most commonly deployed being social media, blogs, and discussion forums. Despite these attempts, the application of technology in supporting international students is still ambiguous. With the reported growing popularity of mobile devices among students and accelerations in learning technology owing to the COVID-19 pandemic, the potential is recognised to address this challenge via the use of chatbot technology. Whilst traditionally, chatbots were deployed as conversational agents in business domains, they have since been applied to the field of education. Within this emerging area of research, a gap exists in addressing the educational value of chatbots over and above the traditional service orientation categorisation. The proposed study seeks to extend upon current understandings by investigating the challenges faced by international students in studying abroad and exploring the potential of chatbots as a solution to assist students’ acculturation. There has been growing interest in the application of chatbot technology to education accelerated by the shift to online learning during the COVID-19 pandemic. Although interest in educational chatbots has surged, there is a lack of consistency in the research area in terms of guidance on the design to support international students in HE. This gap is widened when considering the additional challenge of supporting multicultural international students with diverse. Diversification in education is rising due to increases in migration trends for international study. As global opportunities for education increase, so does the need for multiculturally inclusive learning support.

Keywords: chatbots, education, international students, acculturation

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Authors: Ibragim Issabekov, Byron Crape, Lyazzat Toleubekova

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Background: Palliative care substantially improves the quality of life of terminally-ill patients. Symptom control is one of the keystones in the management of patients in palliative care settings, lowering distress as well as improving the quality of life of patients with end-stage diseases. The most common symptoms causing significant distress for patients are pain, nausea and vomiting, increased respiratory secretions and mental health issues like depression. Aims are: 1. to identify best practices in symptom management in palliative patients in accordance with internationally approved guidelines and compare aforementioned with actual practices in Kazakhstan; to evaluate the criteria for assessing symptoms in terminally-ill patients, 2. to review the availability and utilization of pharmaceutical agents for pain control, management of excessive respiratory secretions, nausea, and vomiting, and delirium and 3. to develop recommendations for the systematic approach to end-of-life symptom management in Kazakhstan. Methods: The use of qualitative research methods together with systematic literature review have been employed to provide a rigorous research process to evaluate current approaches for symptom management of palliative patients in Kazakhstan. Qualitative methods include in-depth semi-structured interviews of the healthcare professionals involved in palliative care provision. Results: Obstacles were found in appropriate provision of palliative care. Inadequate education and training to manage severe symptoms, poorly defined laws and regulations for palliative care provision, and a lack of algorithms and guidelines for care were major barriers in the effective provision of palliative care. Conclusion: Assessment of palliative care in this medium-income transitional-economy country is one of the first steps in the initiation of integration of palliative care into the existing health system. Achieving this requires identifying obstacles and resolving these issues.

Keywords: end-of-life care, middle income country, palliative care, symptom control

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Authors: Héctor González Espinosa, Ricardo Ivan Cordova Chávez, Alejandra Contreras Ramos, Itzia Irene Padilla Martínez, José Guadalupe Trujillo Ferrara, Marvin Antonio Soriano Ursúa

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Boronic acids are able to create diester bonds with carbohydrates because of their hydroxyl groups; in nature, there are some organoborates with these characteristics, such as the calcium fructoborate, formed by the union of two fructose molecules and a boron atom, synthesized by plants. In addition, it has been observed that, in animal cells only the compounds with cis-diol functional groups are capable of linking to boric or boronic acids. The formation of these organoboron compounds could impair the physical and chemical properties of the precursors, even their acute toxicity. In this project, two carbohydrate-derived boron-containing compounds from D-fructose and D-arabinose and phenylboronic acid are analyzed by different spectroscopy techniques such as Raman, Infrared with Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) and X-ray diffraction crystallography to describe their chemical characteristics. Also, an acute toxicity test was performed to determine their LD50 using the Lorke’s method. It was confirmed by multiple spectra the formation of the adducts by the generation of the diester bonds with a β-D-pyranose of fructose and arabinose. The most prominent findings were the presence of signals corresponding to the formation of new bonds, like the stretching of B-O bonds, or the absence of signals of functional groups like the hydroxyls presented in the reagents used for the synthesis of the adducts. The NMR spectra yielded information about the stereoselectivity in the synthesis reaction, observed by the interaction of the protons and their vicinal atoms in the anomeric and second position carbons; but also, the absence of a racemic mix by the finding of just one signal in the range for the anomeric carbon in the 13C NMR spectra of both adducts. The acute toxicity tests by the Lorke’s method showed that the LD50 value for both compounds is 1265 mg/kg. Those results let us to propose these adducts as highly safe agents for further biological evaluation with medical purposes.

Keywords: acute toxicity, adduct, boron, carbohydrate, diester bond

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Authors: Godfrey Muiya Mukala

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This research looks at an array of fields in Sub-Saharan Africa comprising agriculture, food enterprises, medicine, organisms genetically modified, microbiology, and nanotechnology that can be gained from biotechnological research and development. Findings into dangerous organisms, mainly bacterial germs, rickettsia, fungi, parasites, or organisms that are genetically engineered, have immensely posed questions attributed to the biological danger they bring forth to human beings and the environment because of their uncertainties. In addition, the recurrence of previously managed diseases or the inception of new diseases are connected to biosafety challenges, especially in rural set-ups in low and middle-income countries. Notably, biotechnology laboratories are required to adopt biosafety measures to protect their workforce, community, environment, and ecosystem from unforeseen materials and organisms. Sensitization and inclusion of educational frameworks for laboratory workers are essential to acquiring a solid knowledge of harmful biological agents. This is in addition to human pathogenicity, susceptibility, and epidemiology to the biological data used in research and development. This article reviews and analyzes research intending to identify the proper implementation of universally accepted practices in laboratory safety and biological hazards. This research identifies ideal microbiological methods, adequate containment equipment, sufficient resources, safety barriers, specific training, and education of the laboratory workforce to decrease and contain biological hazards. Subsequently, knowledge of standardized microbiological techniques and processes, in addition to the employment of containment facilities, protective barriers, and equipment, is far-reaching in preventing occupational infections. Similarly, reduction of risks and prevention may be attained by training, education, and research on biohazards, pathogenicity, and epidemiology of the relevant microorganisms. In this technique, medical professionals in rural setups may adopt the knowledge acquired from the past to project possible concerns in the future.

Keywords: sub-saharan africa, biotechnology, laboratory, infections, health

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Authors: Anum Javed

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This study identifies the dynamical image of human body that continues its metamorphosis in the virtual field of reality. It calls attention to the ways where humans start co-evolving with other life forms; technology in particular and are striving to establish a realm outside the physical framework of matter. The problem exceeds the area of technological ethics by explicably and explanatorily entering the space of literary texts and criticism. Textual analysis of Geek Love (1989) by Katherine Dunn is adjoined with posthumanist perspectives of Pramod K. Nayar to beget psycho-somatic changes in man’s nature of being. It uncovers the meaning people give to their experiences in this budding social and cultural phenomena of material representation tied up with personal practices and technological innovations. It also observes an ethical, physical and psychological reassessment of man within the context of technological evolutions. The study indicates the elements that have rendered morphological freedom and new materialism in man’s consciousness. Moreover this work is inquisitive of what it means to be a human in this time of accelerating change where surgeries, implants, extensions, cloning and robotics have shaped a new sense of being. It attempts to go beyond individual’s body image and explores how objectifying media and culture have influenced people’s judgement of others on new material grounds. It further argues a decentring of the glorified image of man as an independent entity because of his energetic partnership with intelligent machines and external agents. The history of the future progress of technology is also mentioned. The methodology adopted is posthumanist techno-ethical textual analysis. This work necessitates a negotiating relationship between man and technology in order to achieve harmonic and balanced interconnected existence. The study concludes by recommending a call for an ethical set of codes to be cultivated for the techno-human habituation. Posthumanism ushers a strong need of adopting new ethics within the terminology of neo-materialist humanism.

Keywords: corporeality, dematerialism, human ethos, posthumanism

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Authors: Ledi Neçaj

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Introduction: Cardio-respiratory rehabilitation is the set of coordinated interventions needed to provide the best physical, psychological, and social conditions so that patients with chronic or post-acute cardiopulmonary disease, with their efforts, maintain or resume optimal functioning in society through improved health behaviors. Purpose: To study the effectiveness of the application of Cardio-Respiratory Rehabilitation in the typology of patients with chronic or post-acute cardiomyopathy and chronic respiratory diseases in order to facilitate their therapeutic use and to improve the overall quality of life. Material and Method: This is a prospective study including patients with COPD and cardiac disease who were included in the rehabilitation program during the period January 2019 - November 2021. The study was conducted at the University Hospital Center "Mother Teresa" in Tirana, University Hospital "SHEFQET NDROQI", AMERICAN Hospital, HYGEA Hospital, and "Our Lady of Good Counsel, Tirana". An individual chart was used to collect sociodemographic, physical, clinical, and functional examinations for each patient. Results: The study included 253 patients, with a mean age of 62.1 (± 7.9) years, ranging from 48 to 82 years. (67.6%) of the patients were males, and (32.4%) female. Male patients predominated in all age groups, with a statistically significant difference with females (p<0.01). The most common cardiac pathologies are coronary artery bypass (24%), cerebral stroke (9%), myocardial infarction (17%), Stent placement (8%) (p<0.01). Correlation matrix of risk factors found a significant correlation of alcohol consumption with diabetes, smoking, dyslipidemia, sedentary life, obesity, AVC, and hypertension. Functional capacity estimated by change in metabolic equivalents (MET) improved by 46% from 4. ±2.2 to 7.2± .8 METs (p<0.01). Duration of exercise after rehabilitation was increased by 21% compared to baseline (p<0.01). The mean score of all three subscales of the questionnaire: symptoms (p=0.03), activity (p<0.01), and impact (p<0.01) after rehabilitation, was lower compared to pre-rehabilitation. Conclusions: The rehabilitation program has impacted on improving the quality of life, reducing symptoms, reducing the impact of negative factors on daily life, and reducing dyspnea during daily activities.

Keywords: cardio-respiratory rehabilitation, physical exercise, quality of life, diseases

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Authors: Qunying Yuan, Manjula Bomma, Adrian Rhoden, Zhigang Xiao

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Selenium is an essential micronutrient for all mammals and plays an important role in maintaining human physiological functions. The potential applications of selenium as food supplements, cancer-prevention, antimicrobial and anti-inflammatory agents have been investigated in biomedicine and food sciences. Nanoscale of selenium is of particular interest due to its better biocompatibility, higher bioavailability, lower toxicity, more homogeneous distribution, and presumptive controlled release of substances. The objective of this study is to explore whether selenium nanoparticle (SeNP) has the potential to be used as a food preservative to reduce food spoilage. SeNPs were synthesized through ascorbic acid reduction of sodium selenite using the bovine serum albumin (BSA) as capping and stabilizing agent. The chemically synthesized SeNPs had a spherical conformation and a size of 22.8 ± 4.7 nm. FTIR analysis confirmed that the nanoparticles were covered with BSA. We further tested the antimicrobial activity of these SeNPs against common food-borne bacteria. Colony forming unit assay showed that SeNPs exhibited good inhibition on the growth of Listeria Monocytogens (ATCC15313), Staphylococcus epidermidis (ATCC 700583) starting at 0.5µg/mL, but only a moderate inhibitory effect on the growth of Staphylococcus aureus (ATCC12600) and Vibrio alginolyticus (ATCC 33787) at a concentration higher than 10µg/mL and 2.5µg/mL, respectively. There was a mild effect against the growth Salmonella enterica (ATCC19585) when the concentration reached 15µg/mL. No inhibition was observed in the growth of Enterococcus faecalis (ATCC 19433). Surprisingly, SeNPs appeared to promote the growth of Vibrio parahaemolyticus (ATCC43996) and Salmonella enterica (ATCC49284) at 30 µg/mL and above. Our preliminary data suggested that the chemically synthesized SeNPs may be able to inhibit some food-borne bacteria, and SeNP as a food preservative should be used with caution. We will explore the mechanisms of the inhibitory action of chemically synthesized SeNPs on bacterial growth and whether the SeNPs are able to inhibit the development of biofilm and antibiotic resistance.

Keywords: antimicrobial, food-borne bacteria, nanoparticles, selenium

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Authors: Deepthy Ann Joy, N. Sreedevi

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Hearing impairment (HI) at an early age, identified before the onset of language development can reduce the negative effect on speech and language development of children. Early rehabilitation is very important in the improvement of speech production in children with HI. Other than conventional hearing aids, Cochlear Implants are being used in the rehabilitation of children with HI. However, delay in acquisition of speech and language milestones persist in children with Cochlear Implant (CI). Delay in speech milestones are reflected through speech sound errors. These errors reflect the temporal and spectral characteristics of speech. Hence, acoustical analysis of the speech sounds will provide a better representation of speech production skills in children with CI. The present study aimed at investigating the acoustic characteristics of vowels in Malayalam speaking children with a cochlear implant. The participants of the study consisted of 20 Malayalam speaking children in the age range of four and seven years. The experimental group consisted of 10 children with CI, and the control group consisted of 10 typically developing children. Acoustic analysis was carried out for 5 short (/a/, /i/, /u/, /e/, /o/) and 5 long vowels (/a:/, /i:/, /u:/, /e:/, /o:/) in word-initial position. The responses were recorded and analyzed for acoustic parameters such as Vowel duration, Ratio of the duration of a short and long vowel, Formant frequencies (F₁ and F₂) and Formant Centralization Ratio (FCR) computed using the formula (F₂u+F₂a+F₁i+F₁u)/(F₂i+F₁a). Findings of the present study indicated that the values for vowel duration were higher in experimental group compared to the control group for all the vowels except for /u/. Ratio of duration of short and long vowel was also found to be higher in experimental group compared to control group except for /i/. Further F₁ for all vowels was found to be higher in experimental group with variability noticed in F₂ values. FCR was found be higher in experimental group, indicating vowel centralization. Further, the results of independent t-test revealed no significant difference across the parameters in both the groups. It was found that the spectral and temporal measures in children with CI moved towards normal range. The result emphasizes the significance of early rehabilitation in children with hearing impairment. The role of rehabilitation related aspects are also discussed in detail which can be clinically incorporated for the betterment of speech therapeutic services in children with CI.

Keywords: acoustics, cochlear implant, Malayalam, vowels

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Authors: Ayesha Waqar Khan, Mariam Altaf, Jamil Ahmad, Shaheen Shahzad

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Kidney fibrosis is an anticipated outcome of possibly all types of progressive chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) signaling pathway is responsible for production of matrix-producing fibroblasts and myofibroblasts in diseased kidney. In this study, a discrete model of TGF-beta (transforming growth factor) and CTGF (connective tissue growth factor) was constructed using Rene Thomas formalism to investigate renal fibrosis turn over. The kinetic logic proposed by Rene Thomas is a renowned approach for modeling of Biological Regulatory Networks (BRNs). This modeling approach uses a set of constraints which represents the dynamics of the BRN thus analyzing the pathway and predicting critical trajectories that lead to a normal or diseased state. The molecular connection between TGF-beta, Smad 2/3 (transcription factor) phosphorylation and CTGF is modeled using GenoTech. The order of BRN is CTGF, TGF-B, and SMAD3 respectively. The predicted cycle depicts activation of TGF-B (TGF-β) via cleavage of its own pro-domain (0,1,0) and presentation to TGFR-II receptor phosphorylating SMAD3 (Smad2/3) in the state (0,1,1). Later TGF-B is turned off (0,0,1) thereby activating SMAD3 that further stimulates the expression of CTGF in the state (1,0,1) and itself turns off in (1,0,0). Elevated CTGF expression reactivates TGF-B (1,1,0) and the cycle continues. The predicted model has generated one cycle and two steady states. Cyclic behavior in this study represents the diseased state in which all three proteins contribute to renal fibrosis. The proposed model is in accordance with the experimental findings of the existing diseased state. Extended cycle results in enhanced CTGF expression through Smad2/3 and Smad4 translocation in the nucleus. The results suggest that the system converges towards organ fibrogenesis if CTGF remains constructively active along with Smad2/3 and Smad 4 that plays an important role in kidney fibrosis. Therefore, modeling regulatory pathways of kidney fibrosis will escort to the progress of therapeutic tools and real-world useful applications such as predictive and preventive medicine.

Keywords: CTGF, renal fibrosis signaling pathway, system biology, qualitative modeling

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Authors: Sophio Kobauri, David Tugushi, Vladimir P. Torchilin, Ramaz Katsarava

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Hydrophobic / hydrophilically modified functional polymers are of high interest in modern biomedicine due to their ability to solubilize water-insoluble / poorly soluble (hydrophobic) drugs. Among the many approaches that are being developed in this direction, one of the most effective methods is the use of polymeric micelles (PMs) (micelles formed by amphiphilic block-copolymers) for solubilization of hydrophobic biologicals. For therapeutic purposes, PMs are required to be stable and biodegradable, although quite a few amphiphilic block-copolymers are described capable of forming stable micelles with good solubilization properties. For obtaining micelle-forming block-copolymers, polyethylene glycol (PEG) derivatives are desirable to use as hydrophilic shell because it represents the most popular biocompatible hydrophilic block and various hydrophobic blocks (polymers) can be attached to it. Although the construction of the hydrophobic core, due to the complex requirements and micelles structure development, is the very actual and the main problem for nanobioengineers. Considering the above, our research goal was obtaining biodegradable micelles for the solubilization of hydrophobic drugs and biologicals. For this purpose, we used biodegradable polymers– pseudo-proteins (PPs)(synthesized with naturally occurring amino acids and other non-toxic building blocks, such as fatty diols and dicarboxylic acids) as hydrophobic core since these polymers showed reasonable biodegradation rates and excellent biocompatibility. In the present study, we used the hydrophobic amino acid – L-phenylalanine (MW 4000-8000Da) instead of L-leucine. Amino-PEG (MW 2000Da) was used as hydrophilic fragments for constructing the suitable micelles. The molecular weight of PP (the hydrophobic core of micelle) was regulated by variation of used monomers ratios. Micelles were obtained by dissolving of synthesized amphiphilic polymer in water. The micelle-forming property was tested using dynamic light scattering (Malvern zetasizer NanoZSZEN3600). The study showed that obtaining amphiphilic block-copolymer form stable neutral micelles 100 ± 7 nm in size at 10mg/mL concentration, which is considered as an optimal range for pharmaceutical micelles. The obtained preliminary data allow us to conclude that the obtained micelles are suitable for the delivery of poorly water-soluble drugs and biologicals.

Keywords: amino acid – L-phenylalanine, pseudo-proteins, amphiphilic block-copolymers, biodegradable micelles

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Authors: A. T. Toci, M. V. B. Zanoni

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The advanced oxidation processes have been defined as destructive technologies treatment of wastewater. These involve the formation of powerful oxidizing agents (usually hydroxyl radical .OH) capable of reacting with organic compounds present in wastewater, transforming damaging substances in CO2 and H2O (mineralization) or other innocuous products. However, the photochemical degradation with singlet oxygen has been little explored as oxidative pathway for the treatment of effluents containing food colorants. The molecular oxygen is an effective suppressor of organic molecules in the triplet excited state. One of the possible results of the physical withdrawal is the formation of singlet oxygen. Studies with singlet oxygen (1O2) show an high reactivity of the excited state of the molecule with olefins, aromatic hydrocarbons and a number of other organic and inorganic compounds. Its reactivity is about 2500 times larger than the oxygen in the ground state. Thus, in this work, it was studied the degradation of some dyes used in food industry (tartrazine, sunset yellow, erythrosine and carmoisine) by singlet oxygen. The sensitizer used for generating the 1O2 was methylene blue, which has a quantum yield generation of 0.50. Samples were prepared in water at a concentration of 5 ppm and irradiated with a sunlight simulator (Newport brand, model no. 67005) by consecutive 8h. The absorption spectra of UV-Vis molecules were made each hour irradiation. The degradation kinetics for each dye was determined using the maximum length of each dye absorption. The analysis by UV-Vis revealed that the processes were very efficient for the colorants sunset yellow and carmoisine. Both presented degradation kinetics of order zero with degradation constants 0.416 and 0.104, respectively. In the case of sunset yellow degradation reached 53% after 7h irradiation, Demonstrating the process efficiency. The erithrosine presented during the period irradiated a oscillating degradation kinetics, which requires further study. In the other hand, tartrazine was stable in the presence of 1O2. The investigation of the dyes degradation products owned degradation by 1O2 are underway, the techniques used for this are MS and NMR. The results of this study will enable the application of the cleanest methods for the treatment of industrial effluents, as there are other non-toxic and polluting molecules to generate 1O2.

Keywords: food colourants, singlet oxygen, degradation, wastewater, oxidative

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Authors: Nigatu Tadesse, Ying Liu, Juan Li, Hong Ming Liu

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Gastric carcinogenesis is a lengthy process of histopathological transition from normal to atrophic gastritis (AG) to intestinal metaplasia (GIM), dysplasia toward gastric cancer (GC). The stage of GIM identified as precancerous lesions with resistance to H-pylori eradication and recurrence after endoscopic surgical resection therapies. GIM divided in to two morphologically distinct phenotypes such as complete GIM bearing intestinal type morphology whereas the incomplete type has colonic type morphology. The incomplete type GIM considered to be the greatest risk factor for the development of GC. Studies indicated the expression of the caudal type homeobox 2 (CDX2) gene is responsible for the development of complete GIM but its progressive downregulation from incomplete metaplasia toward advanced GC identified as the risk for IM progression and neoplastic transformation. The downregulation of CDX2 gene have promoted cell growth and proliferation in gastric and colon cancers and ascribed in chemo-treatment inefficacies. CDX2 downregulated through promoter region hypermethylation in which the methylation frequency positively correlated with the dietary history of the patients, suggesting the role of diet as methyl carbon donor sources such as methionine. However, the metabolism of exogenous methionine is yet unclear. Targeting exogenous methionine metabolism has become a promising approach to limits tumor cell growth, proliferation and progression and increase treatment outcome. This review article discusses molecular alterations that could shed light on the potential of exogenous methionine metabolisms, such as gut microbiota alteration as sources of methionine to host cells, metabolic pathway signaling via PI3K/AKt/mTORC1-c-MYC to rewire exogenous methionine and signature of increased gene methylation index, cell growth and proliferation in GIM, with insights to new treatment avenue via targeting methionine metabolism, and the need for future integrated studies on molecular alterations and metabolomics to uncover altered methionine metabolism and characterization of CDX2 methylation in gastric intestinal metaplasia for potential therapeutic exploitation.

Keywords: altered methionine metabolism, Intestinal metaplesia, CDX2 gene, gastric cancer

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Authors: J. Wozniak-Holecka, T. Holecki, P. Romaniuk

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Spa facilities are being perceived as the ways of healing treatment in Poland and are guaranteed within the public financing. The universal health insurance (National Health Fund, NFZ), and the disability prevention programme held by Social Insurance Institution (ZUS) are the main sources of financing spa facilities. The dominant public payer of spa services is the NFZ. The Social Insurance Institution covers the cost of health treatment realized in spa facilities as medical rehabilitation, in the field of disability prevention. Health services delivered in the spa resorts are characterized by complexity, and the combination of various methods, typical for health prevention, education, balneotherapy, and physiotherapy. Healing with natural methods, believed to enhance the therapeutic effect, is also involved in health spa treatment. Regardless of the type of facility, each form of spa treatment includes health promotion, health education, prevention at all levels, including rehabilitation. The aim of the study was to determine the optimal organization of health education process. Its efficiency strongly depends on the type of service provider and the funding institution (NFZ vs ZUS). It results from the use of different measures of the effectiveness, the quality and the evaluation of the process being assessed by funding institutions. The methods of the study include a comparative and descriptive quantitative and qualitative analysis. In the empirical part, a questionnaire had been developed. It was then distributed among spa personnel, responsible directly for the health promotion, and among patients who are beneficiaries of health services in spa centers. The quantitative part of the study was based on interviews carried with the use of the online survey (CAWI: Computer-Assisted Web Interview), telephone survey (CATI: Computer-Assisted Telephone Interview) and a conventional questionnaire (PAPI: Paper over Pencil Interview). As a result of the conducted research, it was found that the effectiveness of health education activities in spa resort facilities in Poland is higher when the services are organized using structured tools for managerial control. This applies to formalized procedures implemented by one of the dominant payers covering costs of services (ZUS) and involves the application of health education as one of the mandatory elements of treatment, subjected to the process of control during the course of spa therapy and evaluation after it is completed.

Keywords: effectiveness, health education, public health system, spa treatment

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Authors: Shouta Sora, Shizuki Kuriu, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

Abstract:

Lymph node (LN) metastasis accounts for 20 - 30 % of all deaths in patients with head and neck cancer. Therefore, the control of metastatic lymph nodes (MLNs) is necessary to improve the life prognosis of patients with cancer. In a classical metastatic theory, tumor cells are thought to metastasize hematogenously through a bead-like network of lymph nodes. Recently, a lymph node-mediated hematogenous metastasis theory has been proposed, in which sentinel LNs are regarded as a source of distant metastasis. Therefore, the treatment of MLNs at the early stage is essential to prevent distant metastasis. Radiation therapy is one of the primary therapeutic modalities in cancer treatment. In addition, total body irradiation (TBI) has been reported to act as activation of natural killer cells and increase of infiltration of CD4+ T-cells to tumor tissues. However, the treatment effect of TBI for MLNs remains unclear. This study evaluated the possibilities of low-dose total body irradiation (L-TBI) and middle-dose total body irradiation (M-TBI) for the treatment of MLNs. Mouse breast cancer FM3A-Luc cells were injected into subiliac lymph node (SiLN) of MXH10/Mo/LPR mice to induce the metastasis to the proper axillary lymph node (PALN) and lung. Mice were irradiated for the whole body on 4 days after tumor injection. The L-TBI and M-TBI were defined as irradiations to the whole body at 0.2 Gy and 1.0 Gy, respectively. Tumor growth was evaluated by in vivo bioluminescence imaging system. In the non-irradiated group, tumor activities on SiLN and PALN significantly increased over time, and the metastasis to the lung from LNs was confirmed 28 days after tumor injection. The L-TBI led to a tumor growth delay in PALN but did not control tumor growth in SiLN and metastasis to the lung. In contrast, it was found that the M-TBI significantly delayed the tumor growth of both SiLN and PALN and controlled the distant metastasis to the lung compared with non-irradiated and L-TBI groups. These results suggest that the M-TBI is an effective treatment method for MLNs in the early stage and distant metastasis from lymph nodes via blood vessels connected with LNs.

Keywords: metastatic lymph node, lung metastasis, radiation therapy, total body irradiation, lymphatic system

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Authors: Zeliha Ustun, Mustafa Ersoz

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In the study, a traditional herbal supplement black cumin seed (Nigella sativa) oil properties has been studied to protect the main quality parameters by a new supplement application. Black cumin seed and its oil is used as a dietary supplement and preferred traditional remedy in Africa, Asia and Middle East for centuries. Now it has been consuming by millions of people in America and Europe as natural supplements and/or phytotherapeutic agents to support immune system, asthma, allergic rinnitis etc. by the scientists’ advices. With the study, it is aimed to prove that soft gelatin capsules are a new and more practical way of usage for Nigella sativa oil that has a longer stability. With the study soft gelatin capsules formulation has been developed to protect cold pressed black cumin seed oil physicochemical properties for a longer period. The product design has been developed in laboratory and implemented in pilot scale soft gelatin capsule manufacturing. Physicochemical properties (peroxide value, free fatty acids, fatty acid composition, refractive index, iodine value, saponification value, unsaponifiable matters) of Nigella sativa oil soft gelatin capsules and Nigella sativa oil in liquid form in amber glass bottles have been compared and followed for 8 months. The main parameters for capsules and liquid form found that for free fatty acids 2.29±0.03, 3.92±0.11 % oleic acid, peroxide 23.11±1.18, 27.85±2.50 meqO2/kg, refractive index at 20 0C 1.4738±0.00, 1.4737±0.00, soap 0 ppm, moisture and volatility 0.32±0.01, 0.36±0.01 %, iodine value 123.00±0.00, 122.00±0.00 wijs, saponification value 196.25±0.46, 194.13±0.35 mg KOH/g and unsaponifiable matter 7.72±0.13, 6.88±0.36 g/kg respectively. The main fatty acids are found that linoleic acid 56.17%, oleic acid 24.64%, palmitic acid 11,94 %. As a result, it is found that cold pressed Nigella sativa oil soft gelatin capsules physicochemical properties are more stable than the Nigella sativa oil stored in glass bottles.

Keywords: black cumin seed (Nigella sativa) oil, cold press, nutritional supplements, soft gelatin capsule

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Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

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Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Reshu Saxena, R. K. Tripathi

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HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.

Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion

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Authors: Naira Sahakyan, Margarit Petrosyan, Armen Trchounian

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One of the tasks in contemporary biotechnology, pharmacology and other fields of human activities is to obtain biologically active substances from plants. They are very essential in the treatment of many diseases due to their actually high therapeutic value without visible side effects. However, sometimes the possibility of obtaining the metabolites is limited due to the reduction of wild-growing plants. That is why the plant cell cultures are of great interest as alternative sources of biologically active substances. Besides, during the monitored cultivation, it is possible to obtain substances that are not synthesized by plants in nature. Isolated culture of Ajuga genevensis with high growth activity and ability of regeneration was obtained using MS nutrient medium. The agar-diffusion method showed that aqueous extracts of callus culture revealed high antimicrobial activity towards various gram-positive (Bacillus subtilis A1WT; B. mesentericus WDCM 1873; Staphylococcus aureus WDCM 5233; Staph. citreus WT) and gram-negative (Escherichia coli WKPM M-17; Salmonella typhimurium TA 100) microorganisms. The broth dilution method revealed that the minimal and half maximal inhibitory concentration values against E. coli corresponded to the 70 μg/mL and 140 μg/mL concentration of the extract respectively. According to the photochemiluminescent analysis, callus tissue extracts of leaf and root origin showed higher antioxidant activity than the same quantity of A. genevensis intact plant extract. A. genevensis intact plant and callus culture extracts showed no cytotoxic effect on K-562 suspension cell line of human chronic myeloid leukemia. The GC-MS analysis showed deep differences between the qualitative and quantitative composition of callus culture and intact plant extracts. Hexacosane (11.17%); n-hexadecanoic acid (9.33%); and 2-methoxy-4-vinylphenol (4.28%) were the main components of intact plant extracts. 10-Methylnonadecane (57.0%); methoxyacetic acid, 2-tetradecyl ester (17.75%) and 1-Bromopentadecane (14.55%) were the main components of A. genevensis callus culture extracts. Obtained data indicate that callus culture of A. genevensis can be used as an alternative source of biologically active substances.

Keywords: Ajuga genevensis, antibacterial activity, antioxidant activity, callus cultures

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Authors: Sohail Bawani, Kausar S. Khan, Rozina Karmaliani, Shehnaz Mir

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Action research (AR) is one of the types of health systems research (HSR), and participatory action research (PAR) is known for being effective in health systems strengthening (HSS). The current literature on PAR for HSS cites numerous examples and case studies that led to improve health services; build child health information system; increase knowledge and awareness of people about health problems, and identify pathways for institutional and policy change by engaging people in research. But examples of marginalized communities being agents of change in health governance are not common in health systems research (HSR). This approach to PAR is at the heart of Paolo Freire’s Social Transformation Theory and Critical Consciousness building, which was used to design a community-based PAR study in the Northern/mountainous areas of Pakistan. The purpose of the study was to understand the place and role of marginalized communities in strengthening existing health governance structure (health facility and village health committees and health boards) by taking marginalized communities as partners. Community meetings were carried out to identify who is living at the social, political, cultural and economic margins in 40 different villages. Participatory reflection and analysis (PRA) tools were used during the meeting to facilitate identification. Focus group discussions were conducted with marginalized groups using PRA tools and family ethnographies with marginalized families identified through group discussions. Findings of the study revealed that for the marginalized health systems constitute more than just delivery of health services, but it also embraces social determinants that surround systems and its governance. The paper argues that from Frerian perspective people’s participation should not only be limited to knowledge generation. People must be seen active users of the knowledge that they generate for achieving better health outcomes that they want to achieve in the time to come. PAR provides a pathway to the marginalized in playing a role in health governance. The study dissemination planned shall engage the marginalized in a dialogue with service providers so that together a role for the marginalized can be outlined.

Keywords: participatory action research, health systems, marginalized, health services

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Authors: Philip Friedlander, John Rutledge, Jason Suh

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Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

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