bluuebunny/crossref_metadata_2025 huggingface dataset:
Arsonium and phosphonium-functionalized gold nanoparticles for mitochondria targeted therapeutics
Authors:   , Lalwani Nikhil Narendra
Published: April 2024

This thesis presents a body of original research describing the synthesis, characterisation and biological properties of novel arsonium- and phosphonium- alkylthiosulfate zwitterions and thioacetate salts and gold nanoparticles functionalized with triphenylarsoniumpropylthiolate ligands. Chapter 1 presents a systematic literature review of the preparation of functionalized gold nanoparticles, their biomedical properties, the biological applications of phosphonium and arsonium ions and phosphonium-functionalized nanomaterials. Details of the analytical methods employed to characterize all the compounds produced in this study are outlined in chapter 2. Chapter 3 reports the synthesis of the triphenylarsoniopropylthiosulfate zwitterion and ω- thioacetylpropyl(triphenyl)arsonium bromide salt. Both compounds have been characterized spectroscopically and by single crystal X-ray diffraction. The thiosulfate group of the triphenylarsoniopropylthiosulfate zwitterion and the thioacetate group of the ω- thioacetylpropyl(triphenyl)arsonium salt undergo reductive cleavage, forming the corresponding triphenylarsoniumpropylthiolate ions that attach to the surface of gold in a modification of the established Brust-Schiffrin method for preparing gold nanoparticles. TEM studies show the triphenylarsonium-functionalized gold nanoparticles to be spherical with diameters of c.a. 3nm. The presence of the triphenylarsonium groups has been confirmed by Raman and XPS spectroscopy and mass spectrometry. It also describes the synthesis, characterisation and biological properties of a family of phosphoniopropylthiosulfate zwitterions and ω-thioacetylpropyl(triaryl)phosphonium salts derived from tri(4-methoxyphenyl)phosphine, tri(2,6-dimethoxyphenyl)phosphine and tri(2,4,6-trimethoxyphenyl)phosphine. The IC50 values of the triphenylarsoniopropylthiosulfate zwitterion, ω-thioacetylpropyl- (triphenyl)arsonium bromide salt, triphenylarsonium-functionalized gold nanoparticles and family of phosphoniopropylthiosulfate zwitterions and ω- thioacetylpropyl(triaryl)phosphonium salts derived from tri(4-methoxyphenyl)phosphine, tri(2,6-dimethoxyphenyl)phosphine and tri(2,4,6-trimethoxyphenyl)phosphine have been determined against PC3 prostate cancer cells using MTT and CellTiter-Glo assays and are reported in Chapter 4. The uptake of the triphenylarsonium-functionalized gold nanoparticles by PC3 and Human Fibroblast cells has also been determined by ICP-OES spectroscopy.
The Role of an Online Community in Supporting Diabetes Self-Management in Thailand
Authors:   , Boonchum Nittaya
Published: April 2024

One of the greatest health issues facing the world today is diabetes mellitus (diabetes), and Thailand is no exception. Even though diabetes cannot be cured, those who manage their illness well can have normal lives. To effectively monitor and regulate their blood sugar levels, people with diabetes must spend a significant amount of time working on self-management outside of medical settings. Most patients fail to complete this procedure because it is patient-centred, meaning that patients must complete it primarily on their own. Since questions or problems with their diabetes treatment could arise at any time, they search online for support. In addition to providing users with constant access to information about diabetes self-management, online forums allow users the chance to connect with others, exchange stories, ask questions, and seek assistance. The aim of this thesis is to examine the ways in which people use the online community Pantip to exchange their knowledge and experience as part of the self-management of diabetes and as carers, as part of an overall strategy of managing diabetes, and to explore the cultural context for diabetes self-management in Thailand. The analysis examines 992 individual posts in 177 message threads during a period of 6 months on a message board on Pantip and the interviews with 15 members of the forum. A thematic analysis was conducted to identify major themes related to the diabetes self-management. According to the study, the site helps users with peer support, informational support, and emotional support, particularly when it comes to lifestyle management, which is the self-manager's main area of the problem. Users of Pantip also consider how Thai culture either encourages or discourages self-management. While Thai cuisine can be a barrier to diet control, which may lead people with diabetes to utilize complementary and alternative therapies, Thai family structures promote the adult child's role as a carer in Thailand.Even though Thailand permits the use of both conventional medicine and complementary and alternative medicine (CAM), most patients never discuss their use of CAM with their doctors; they choose to discuss it online. Pantip acts as a resource for individuals, helping them understand why they use it, assisting in rechecking it, and providing advice to caution against latent advertising. For carers, Pantip is a place to learn about the responsibilities of caring for people with diabetes and how to deal with crises or struggles by receiving both informational and emotional support.Overall, the community supports patient-centred approaches that are the cornerstone of diabetes management by sharing experiences that provide insights into how people with diabetes deal with their diseases and how Thai culture affects self-management. Pantip, an online community, can help people with diabetes and their carers practice better self-management, which may improve their health outcome.
Expectations regarding interpreters in Brazil in the light of pandemic-enforced technological change: A pilot study
Authors: Machado Renata , Downie Jonathan
Published: April 2024

This article examines stakeholder expectations of interpreters in the Brazilian legal system and how they may have changed with the shift to remote interpreting during the pandemic. The study explores stakeholder expectations of interpreters and the interplay of these expectations with the growth of remote interpreting. To do so, it builds on the growing awareness of the need to rethink the methods used to understand stakeholder expectations. The study is based on questionnaires administered to judges, prosecution, and defence lawyers, as well as interpreters themselves. These questionnaires explored their reactions to vignettes adapted from real-life experience and to specific questions, comparing the responses from both methods. The results revealed how remote interpreting has increased tensions between the perceived needs of interpreters and the perceived demands of those involved in the legal process. This article argues that interpreters’ expectations hinge on the concept of “linguistic presence,” a concept with different meanings for language professionals and legal professionals. The discrepancy is especially pertinent given the growth of remote interpreting and how it may impact the presence of the interpreter.
The incidence of empathy when interpreting in the field for vulnerable populations in the Israeli-Palestinian conflict
Authors: Barea Muñoz Manuel
Published: April 2024

This article describes the incidence of empathy in field interpreters who work with vulnerable populations in the context of the Israeli-Palestinian conflict. Qualitative data was gathered via interviews conducted in 2018 with professional field interpreters working for international organizations (both freelancers and staffers), resulting in two paradigmatic narratives (one for each professional profile) aimed at preserving the participants’ anonymity. The narratives reveal a significant incidence of empathy in certain communicative situations, and views of empathy as both a hindrance and a useful emotion for the task at hand. The article suggests that such conflicting perceptions may be addressed empowering field interpreters to reconcile themselves with their own positionality through psychological training.
Vulnerability, moral concepts, and ethics in interpreting
Authors: Yuan Xiaohui
Published: April 2024

While many studies have been conducted to investigate types of role that interpreters take on to represent and advocate for vulnerable populations, interpreters’ vulnerability and its source in this particular type of encounter are rather under-explored. Interpreting for vulnerable populations is conceptualised in this study as a distinct communicative context riddled with institutional, knowledge, and power politics that gives rise to emotive, nuanced, and subjective moral judgements on the obligation of care. Drawing from theories in vulnerability studies and from moral concepts, and employing the interpretative phenomenological analysis (IPA) methodology, the author, with three professional public service interpreters, explores the key factors contributing to their situational vulnerability, the driving forces motivating their decision to support agency, the adverse effects on the interpreters attributed to the situational vulnerability of moral distress, and how to recontextualise ethics guiding interpreting for vulnerable populations. This constitutes the first study theorising the public service interpreter’s situational vulnerability, and how interpreters’ decisions are influenced by the interdependency between facets of vulnerability and moral concepts.
“I faced so many barriers”: Access to support for deaf female survivors of domestic violence in the UK
Authors: Napier Jemina , Clark Lucy , Leeson Lorraine , Quigley Lianne
Published: April 2024

This article examines the potential vulnerability of deaf female British Sign Language (BSL) signers who experience domestic violence (DV) in reporting DV and accessing information and communication support. Based on online semi-structured interviews with eight deaf women in the UK, their perceptions of the factors that contribute to creating barriers in gaining adequate access and support are discussed. We present findings that concentrate around seven key barriers identified by the interviewees including: (i) access to interpreting; (ii) lack of information in BSL; (iii) lack of deaf cultural awareness; (iv) needs for on-going support; (v) deaf-specific services; (vi) training/education needs; and (vii) recognition of diversity. In considering deaf women’s reporting of DV incidences through an intersectional lens, it is clear that they experience a double, or even triple or quadruple disadvantage. We found that, despite professional interpreting services being widely available in the UK, structural barriers still exist for deaf women in gaining access to support for DV, and that barriers are created through inaccessible services, inaccessible information, and lack of awareness of the needs of deaf women in this context. These barriers can be mitigated through training and resources for sign language interpreters, police officers, and other support service providers. We conclude with suggestions for how this research can be applied to interpreting for female DV survivors in other minority communities as well as deaf communities, with suggestions for further research.
Asylum hearings in Italy: Who mediates between cultures?
Authors: Amato Amalia Agata Maria , Gallai Fabrizio
Published: April 2024

According to several legal scholars and practitioners, the most crucial factor for refugee status determination (RSD) is whether or not asylum seekers can provide credible evidence of a “well-founded fear” of persecution. However, this adjudication process is extremely complex as psychological, linguistic, and general cultural factors have a substantial impact on credibility. Through examining interpreter-mediated asylum hearings in Italy, our aim is to bring to the fore the interconnections between asylum interpreting practices and (inter)cultural factors. More specifically, emphasis will be put on the roles of communication and culture to elucidate how interpreting enables and restrains asylum seekers in their efforts to establish themselves as deserving of protection. We argue that culturally-bound norms negatively and unevenly influence the outcomes of some asylum cases and support this claim with evidence from interpreter-mediated hearings with asylum seekers and immigration officers in central Italy. In order to analyse this data, we adopt an interaction- and discourse-centred approach. Training for interpreters working in this environment and improving the quality of asylum interpretation services will ultimately lead to fairer refugee status determination procedures and better professional ethics for interpreters.
Formação continuada de professores enquanto lócus para avaliação de produto educacional
Authors: Fragoso Marco Aurelio Soares , De Morais Josmaria Lopes , Romero Adriano Lopes
Published: April 2024

O presente trabalho parte da premissa de que os professores que atuam na Educação Básica podem desempenhar o papel de receptores e avaliadores dos produtos educacionais (PEs) em fase de desenvolvimento. Neste contexto, o presente trabalho teve como objetivo avaliar um PE com abordagem Ciência-Tecnologia-Sociedade-Ambiente (CSTA) por professores de Química em formação continuada. Trata-se de uma sequência didática (SD), sobre o objeto de conhecimento tabela periódica, elaborada considerando os parâmetros e propósitos educacionais da abordagem CTSA. A etapa de avaliação desse PE, realizada no contexto de um curso de formação continuada, contou com a participação de sete professoras da rede estadual de ensino do Paraná. Utilizando questionários como instrumento de coleta de dados, realizaram-se 13 questões agrupadas em três categorias, que se relacionam com o uso da abordagem CTSA e percepções quanto à presença de parâmetros e propósitos educacionais da abordagem CTSA na SD. Ficou evidente, a partir das respostas das professoras, que, ao explorar o artefato tecnológico smartphone, utilizando a abordagem CTSA, o ensino do objeto de conhecimento tabela periódica poderá ser melhor compreendido e valorizado pelos estudantes da Educação Básica. Quanto à presença dos parâmetros e propósitos educacionais da abordagem CTSA, as participantes pontuaram que os recursos e as ferramentas apresentados na SD contribuem para alcançar os objetivos elencados para cada uma das unidades propostas. Ao final da pesquisa, destacamos a importância de considerar os professores da Educação Básica para além de potenciais usuários dos PEs, incluindo-os como agentes ativos nas etapas de implementação e avaliação de PEs.
Conhecimento como criação
Authors: Oliveira André
Published: April 2024

O presente ensaio propõe a hipótese de que, no contexto educacional, fundamentos anti-cartesianos sobre conhecimento oferecem possibilidades de subversão de tecnologias para arrefecimento das estruturas de opressão, controle e dominação. A partir de metodologia de revisão bibliográfica o ensaio relaciona assuntos como ciência cognitiva e estudos decoloniais para pensar  dois casos de tecnologias educacionais e suas implicações políticas. Para alcançar esses objetivos o texto articula-se em três partes. A primeira delas descreve a noção de conhecimento, fundamento para quaisquer discussão sobre aprendizagem ou ensino, no contexto da área de ciência cognitiva. A etapa seguinte discute a relação entre ferramentas educacionais de tempos diferentes e seus fundamentos conceituais cartesianos enquanto definidores de suas políticas e histórias de uso. Uma terceira parte encaminha relações e conclusões sobre possibilidades de subversão da ordem colonizadora. Nessa etapa apresenta-se um caminho de emancipação por meio da desobediência e da criação de formas de utilizar ferramentas educacionais para narrar as próprias histórias na periferia do capitalismo.
Formação de professores em cursos normais superiores
Authors: Küster Eliane , Vieira Alboni Marisa Dudeque Pianovski
Published: April 2024

O artigo teve por objetivo analisar a produção científica acerca da formação de professores em cursos normais superiores, no intuito de elencar o que vem sendo produzido nessa área, averiguar a evolução e as características das pesquisas e identificar recorrências e lacunas pertinentes a temática. A pesquisa foi realizada na modalidade “estado do conhecimento”, com apoio em Morosini (2015) e Romanowski e Ens (2006). Sob o ponto de vista metodológico, o estudo teve caráter bibliográfico e documental, com abordagem qualitativa. O corpus de análise foi composto por produções brasileiras exportadas da Biblioteca Digital Brasileira de Teses e Dissertações (BDTD) e do Catálogo de Teses e Dissertações da CAPES. O recorte temporal foi estabelecido entre 2003 e 2016, em consonância com as datas de publicação dos documentos disponíveis para consulta. No decurso da análise, emergiram duas categorias (teoria e prática pedagógica na formação de professores e formação de professores na perspectiva da história da educação e das políticas educacionais), das quais afloraram cinco subcategorias, que favoreceram a averiguação das produções selecionadas. A pesquisa permitiu refletir sobre a organização da educação no país, políticas educacionais responsáveis pela institucionalização da formação de professores e práticas pedagógicas. Os resultados demonstraram que os cursos normais superiores, em suas breves trajetórias, tiveram relevância na história da educação brasileira.
Contribuições de Bernardete Angelina Gatti à pesquisa sobre formação de professores no Brasil
Authors: Schlindwein Luciane Maria , De Souza e Souza Maria Luiza , Gonçalves Daniela Fonseca
Published: April 2024

Este artigo apresenta a professora e pesquisadora Bernardete Angelina Gatti, com o intuito de discutir suas contribuições no campo da pesquisa educacional brasileira, sobretudo no campo da formação de professores, da avaliação e da metodologia científica. Para elaboração deste texto realizamos uma pesquisa sobre a produção bibliográfica de Bernardete, analisando seu currículo lattes e outras plataformas, tais como Scielo, Google Scholar, Portal da Anped. Pautamos nosso estudo na leitura de textos produzidos sobre ela e, ainda, sobre as lives proferidas por ela ao longo da pandemia do Covid-19. Além disto, fizemos um convite à Bernardete para que ela indicasse publicações, sobretudo livros, que pudessem colaborar com nosso exercício de reflexão sobre a produção científica desta pesquisadora preocupada e comprometida com a formação de professores no Brasil.
Iria Brzezinski
Authors: Tozetto Susana Soares , Volkman Elizabete
Published: April 2024

O presente artigo apresenta elementos da caminhada profissional da Profa. Dra. Iria Brzezinski, com o objetivo de revisitar a trajetória de vida e da obra da autora, enfatizando os aspectos biográficos como professora, pesquisadora e militante. A biografia da professora Iria Brzezinski é permeada pelo misto entre a carreira docente, a militância política em defesa da formação de professores e o contexto histórico vivenciado pela sociedade. Para o presente artigo, julgamos necessário escrever sobre a trajetória de vida e sobre as pesquisas da professora Iria Brzezinski, enfatizando três aspectos que se complementam: os eventos da vida da autora; a relação de sua história de vida com o contexto histórico em que iniciou suas pesquisas; e a relação entre suas pesquisas, sua militância política e a sua defesa pela formação dos profissionais da Educação. As pesquisas de Iria Brzezinski contribuíram de modo significativo para a área de formação de professores, tanto no debate para as diretrizes dos cursos de licenciatura, como nas reflexões sobre os conceitos de docência, de formação inicial, formação continuada, formação tecnocrata e, ainda, para as concepções de identidade do pedagogo e da Pedagogia. As contribuições da autora para a área educacional são inegáveis, Brzezinski formulou definições que contribuíram para a reformulação do curso de Pedagogia e, consequentemente, dos demais cursos de licenciatura, defendendo ideias e conceitos que marcaram a trajetória da Educação no Brasil.
CALCULATION OF REDUCED IONIZATION COEFFICIENT AND DEMONSTRATION OF OBTAINING CROSS SECTION SETS USING SWARM METHOD ON AN EXAMPLE OF NEON GAS
Authors: Budiša Dragana , Duplјanin Snježana
Published: April 2024

This paper presents the use of swarm method for obtaining sets of cross sections on an example of Neon gas (Ne). Cross sections for e-/Ne interaction available in the LxCat database were presented and discussed. The following three bases were selected: Biagi-v7.1, Morgan and Siglo. We used Bolsig+ code to calculate reduced ionization coefficient (α/N), after which calculated values were compared to measured values in the Dutton base. The swarm method was demonstrated in the α/N example, where the Morgan cross sections set was used as an entry parameter for calculation of coefficient.
DETERMINATION OF CHLORIDE CONTENT IN BOTTLED MINERAL WATER
Authors: Blagojević Dragana , Polovina Andrea , Lazić Dragica , Jelić Dijana
Published: April 2024

Mineral waters from different sources have different contents, because each source has its own individual physical and chemical characteristics. Chlorides appear in natural waters because of the dissolution of minerals from sediments, but also because of anthropogenic influence. In this paper, Mohr's method of chloride content determination was used. Natural mineral waters “aqua viva” and “ELEMENT” were used for testing. Determination by Mohr’s method was performed in water samples without the addition of standard and with the addition of standard, as well as in the standards themselves. In water samples without the addition of standards, much higher chloride content values were obtained than those given by the declaration. The results of the Recovery test obtained after the determination of chloride content in the samples with the addition of the standard confirmed the applied method for the used concentration range. Based on the difference in the chloride content in the samples with the addition of standard and the standards themselves, the values of the chloride content in the sample were determined and they were closer to the values stated on the declaration. Given the results of the performed analyses, it can be concluded that they are in agreement with literature data, i.e. Mohr’s method is more suitable for determination in samples with high chloride concentrations. In samples containing low concentrations of chloride, a tendency towards increased results was recorded, which was also the case in this research.
AMPHIBIANS OF RAMSAR SITE “BARDAČA WETLAND” – A CHECKLIST WITH ECOLOGICAL NOTES
Authors: Šukalo Goran , Dmitrović Dejan
Published: April 2024

The goal of this study was to create a faunistic list of amphibians of the Ramsar site "Bardača Wetland" based on literature data and original field studies by the authors, with reference to certain aspects of the ecology of the recorded species. Field data were collected using the transect method, in the period from 2012 to 2022, providing data on nine species of amphibians. Presence of five species previously cited in literature sources was not confirmed. Therefore, the batrachofauna of the Ramsar site "Bardača Wetland" reliably consists of nine species of amphibians: two species of caudate amphibians (Lissotriton vulgaris and Triturus dobrogicus) and seven species of anurans (Bombina bombina, Bufo bufo, Bufotes viridis, Hyla arborea, Pelophylax kl. esculentus, Pelophylax ridibundus and Rana dalmatina). In this paper, the ecological data collected in the field (habitat types of adults and larvae, the season of their activity within the annual cycle, general state of populations of some species) and corresponding ecological data from literature sources are systematically presented, separately for each species.
FAUNISTIČKI NALAZI SA PLANINE VOLUJAK: PRILOG POZNAVANJU FAUNE REPUBLIKE SRPSKE (BOSNA I HERCEGOVINA)
Authors: Trbojević Igor , Dmitrović Dejan
Published: April 2024

Predstavljeni su prvi, nakon dugog perioda bez bilo kakvih naučnih istraživanja, faunistički nalazi sa područja masiva Volujka (jugoistok Republike Srpske, Bosna i Hercegovina). Pored popisa diverziteta faune sisara, zabilježeni su podaci i o drugim faunističkim grupama (ptice, gmizavci, vodozemci, ribe i beskičmenjaci). Različite metode su korištene za otkrivanje prisustva faune istraživanog područja: uspostavljeni linijski transekati, hvatanje živolovkama, mreže za hvatanje šišmiša, snimanje organizama ultrazvučnim detektorom i foto-zamkama i vizuelno osmatranje. Za 17 dana istraživanja, u julu i avgustu 2023., ukupno su registrovana 53 taksona životinja. Izdvajaju se ključne i ugrožene vrste: veliki potkovičar (Rhinolophus ferrumequinum), mali potkovičar (Rhinolophus hipposideros), sivi vuk (Canis lupus), mrki medvjed (Ursus arctos), balkanska divokoza (Rupicapra r. balcanicus), šargan (Vipera ursinii macrops) i bukova strižibuba (Morimus funereus). Područje je biodiverzitetski veoma značajno, i smatra se da ga treba zaštititi.
FANEROFITE U FLORI BILEĆE (REPUBLIKA SRPSKA, BOSNA I HERCEGOVINA)
Authors: Marić Nataša , Petronić Slađana , Radovanović Anđela
Published: April 2024

U radu su prikazani rezultati istraživanja dendroflore područja opštine Bileća. Floristička istraživanja vršena su tokom vegetacijske sezone 2017. i 2018. godine. Potvrđeno je prisustvo 114 vrsta i podvrsta bilјaka, grupisanih u 73 roda i 35 porodica. U pogledu životnih formi dominiraju fanerofite iz grupe listopadnog drveća. Prema bilјnogeografskoj analizi najčešće su vrste iz submediteranske, evroazijske i subatlantske areal grupe. Analizom ekoloških indeksa za osnovne ekološke faktore utvrđena je dominacija submezofita. Većina taksona preferira neutrofilnu do bazofilnu reakciju zemlјišta, koje je siromašno hranlјivim materijama. U odnosu na svjetlost najbrojnije su poluskiofite, odnosno bilјke polusjene, dok u odnosu na temperaturu dominira grupa smještena na prelazu, između mezotermnih i termofilnih bilјaka.
Development of tactical skills in handling automatic firearms among cadets and students of educational organizations of the Ministry of Internal Affairs of Russia
Authors: Vasil'ev Mikhail Aleksandrovich , Kleimenov Semen Yur'evich
Published: April 2024

The object of the research of the article is the tactical basics of handling automatic firearms during fire training. The subject of the research is the tactical basics of possession of automatic firearms during the training of fire arms handling. The purpose of the study is to identify the most effective methods for conducting fire training classes aimed at developing handling skills of the students. Research aim is to determine the most effective and accessible methods in the process of handling automatic firearms. The practical significance of the conducted research consists in identifying the most effective methods for fire training training, necessary for practical application. At the same time, attention is paid to strict compliance with safety measures when handling both training and combat weapons during training. The methodology of the conducted research is determined by its purpose and objectives. It is based on a systematic approach to the study of methods of training police officers in the practical use of firearms. The novelty of the scientific article lies in the development of author's methods in the study and testing of tactical actions of cadets and students of educational organizations of the Ministry of Internal Affairs of Russia in the handling of automatic firearms during fire training. When practicing tactical skills, actions with automatic firearms were carried out both idling and during live firing. The training exercises were practically tested during the training of cadets and trainees at the stage of the practical part of fire training. The development of tactical actions allowed the trainees to form confident practical skills in handling automatic firearms, which in turn affected the increase in the level of general discipline and the readiness of employees to act in practice.
Development of self-nanoemulsifying drug delivery system of 1-(2,5-dihydroxy phenyl)-3-pyridine-2-yl-propenone to enhance pro-apoptotic activities in MCF-7 breast cancer cells
Authors: Edityaningrum Citra Ariani , Wibowo Andy Eko , Arimurni Dewa Ayu , Rahmawati Yulia , Fatimah Siti Fatmawati , Novitasari Laras , Khoirunnisa Siti
Published: April 2024

Compound 1-(2,5-dihydroxy phenyl)-3-pyridine-2-yl-propenone is a derivative of 2′,5′-dihydrochalcone, with a 2-pyridine substitution in B ring. Several studies showed that it is an effective anti-inflammatory and anti-cancer agent. However, its low water solubility limits its therapeutic applications and bioavailability. Therefore, 1-(2,5-dihydroxy phenyl)-3-pyridine-2-yl-propenone was formulated into self-nano-emulsifying drug delivery systems (SNEDDS), to improve its solubility and bioavailability. A total of three formulas, F1 (10%:67.5%:22.5%), F2 (15%:63.75%:21.25%), and F3 (20%:60%:20%) were developed with variation in olive oil as the oil phase, tween 80 and PEG 400. The optimal formula was determined based on the droplet size, polydispersity index (PDI), and emulsification time. It was then further evaluated for its zeta potential, drug loading capacity, and cytotoxic activity toward MCF7 cells using [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium-bromide] assay. Among the three formulations, F1 produced more suitable physicochemical characteristics, such as a low droplet size of 11.06 ± 0.06 nm, PDI of 0.10 ± 0.02, and ability to self-emulsify into nanoemulsion within 10.51 ± 0.45 seconds. It also had a good zeta potential of −16.24 ± 2.40 mV with a maximum loading capacity of 6 mg drug per 1 g of SNEDDS. The IC50 toward MCF7 cells for F1 was 5.3 μg/ml which shows moderate cytotoxic activity. It also modified the cells’ morphology which led to a decrease in cancer cells’ viability. Based on these results, SNEDDS 1-(2,5-dihydroxy phenyl)-3-pyridine-2-yl-propenone has been successfully formulated and potential as a carrier that is effective against MCF7 cells.
Anticancer activity of Celtis tournefortii Lam. against human liver cancer cells
Authors: Nadiger Kavitha Krishna , Gunam Valli , Kalyanaraman Rajagopal , Balakrishnan Meenashree , Revathi Kasturi , Narasimma Barathy Sathya T.
Published: April 2024

Celtis tournefortii Lam. (Celtis aetnensis) is a species of plant with extraordinary bioactivities that has received little research and documentation. Its potential to treat human liver cancer has not yet been studied. Therefore, the bark extract was tested in vitro against human hepatocellular carcinoma (HepG2) cells in the current investigation. The extract was found to increase the Reactive Oxygen Species (ROS) levels in tumor cells, causing cytotoxicity. In addition, the lactate dehydrogenase level was found to be elevated, indicating cellular damage. The likelihood that C. tournefortii Lam. will target the AKT protein is suggested by a considerable drop in the expression of the AKT gene. This is the first report on the effectiveness of C. tournefortii Lam. against liver cancer reported thus far. Our results suggest the presence of promising therapeutic compounds in the bark of C. tournefortii Lam.
Inhibitory effect of 14 essential oils against resistant pathogenic bacteria and fungi and chemical compositions of selected essential oils
Authors: Aviwe Khuzani , Phozisa Deli , Egbichi Ifeanyi , Kaptchouang Christ-Donald Tchatchouang , Manganyi Madira
Published: April 2024

Current antimicrobial agents have become useless against multidrug-resistant pathogens. There is a necessity to discover novel antimicrobial compounds to combat these pathogens. The global trend promotes a greener and more sustainable alternative, such as essential oils (EOs). EOs are complex volatile bioactive compounds, which assist plants in the defense against pests and pathogens. A total of 14 EOs were tested for antibacterial and antifungal activity against resistant pathogens. The thyme EO completely inhibits the plant pathogenic fungi at all concentrations (100% inhibition), followed by cinnamon which completely inhibits all plant pathogens at 500 and 1,000 μl/l concentration (100% inhibition). While lemongrass was the most active EO against all bacteria except for Enterococcus caecium, it had the highest zone of inhibition (22 mm) against Mannheimia haemolytica. Tea tree was the second active EO. Thyme was the most sensitive EO against all pathogenic bacteria except for Listeria monocytogenes (ATCC 19115) and Salmonella enterica. In conclusion, there is strong evidence that EOs provide a suitable sustainable alternative to conventional therapeutic agents, which could decrease the minimum effective dose of the drugs, thus reducing their possible adverse effects and the costs of treatment.
Modulatory effect of ethylacetate fraction from Theobroma cacao pod husk on blood pressure in L-NAME-induced hypertensive rats using in vivo and in silico approaches
Authors: Nwaso-Sunday Elizabeth Oyabebefa , Adeoye Raphael Idowu , Olasehinde Oluwaseun Ruth , Afolabi Olakunle Bamikole , Arise Rotimi Olusanya
Published: April 2024

Hypertension related diseases are public health concerns due to their high incidence and mortality. However, the inability of the synthetic drugs to normalize blood pressure (BP) to acceptable range has motivated the search for safer and effective alternatives. This study investigated the antihypertensive activity of ethyl acetate fraction of Theobroma cacao pod husk (EAF-TCPH) in L-nitro-arginine-methyl-ester (L-NAME)-induced hypertensive male rats. Methanol extract of Theobroma cacao pod husk (TCPH) was partitioned to obtain the EAF-TCPH fraction. Hypertension was induced by oral administration of 40 mg/kg body weight (bw) L-NAME; while BP was checked by tail plethysmography. Wistar rats were assigned into groups 1–6. Group 1 received 1.0 ml of paraffin oil, while groups 2–6 were hypertensive rats and received 1.0 ml of paraffin oil, 12.5, 25 and 50 mg/kg bw of the EAF-TCPH and 25 mg of captopril respectively for 6 weeks. The compounds in EAF-TCPH were identified using high performance liquid chromatography and were docked against angiotensin converting enzyme (ACE). Elevated BP of 180.17 (systolic) and 125.79 mmHg (diastolic) in the hypertensive rats was lowered to 125.33 and 88.00 mmHg, respectively in the 25 mg/kg bw EAF-TCPH treated group. The major compounds in EAF-TCPH were theaflavin, epigallocatechin, procyanidin, epicatechin and cianidanol. Theaflavin binds to ACE better than captopril (standard drug) with binding energy of −10.8 and −5.8 kcal/mol, respectively. This study therefore suggests that EAF-TCPH could have demonstrated potential antihypertensive activities in L-NAME-induced hypertensive rats due to the available bioactive components in EAF-TCPH that probably interacted in a beneficial way with ACE.
Green precipitation method using Polyscias scutellaria extract in the synthesis of hydroxyapatite/alginate/copper (II) oxide composites as a drug carrier
Authors: Wulandari Wulandari , Jamarun Novesar , Wellia Diana Vanda , Emriadi Emriadi
Published: April 2024

Hydroxyapatite (HAp) is a bioceramic naturally present in human bones and teeth, prized for its exceptional biocompatibility, bioactivity, and capacity for osteointegration, rendering it a viable candidate for biomedical applications as a drug delivery system. Nevertheless, HAp possesses limited antibacterial properties. Thus, the present study focuses on synthesizing HAp/alginate/copper oxide (HAp/Alg/CuO) composite to augment these attributes. An environmentally friendly synthesis approach is explored to create the HAp/Alg/CuO composite. Polyscias scutellaria leaf extract is anticipated to function as a capping agent, facilitating control over the composite’s morphology. In addition, residual bamboo clam shells serve as the precursor material for HAp fabrication. The composites prepared were analyzed by a series of characterization techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS). XRD analysis revealed the formation of HAp/Alg/CuO composites exhibiting a hexagonal structure consistent with the ICSD (The inorganic Crystal Structure Database) #157481 standard. The crystallite size was obtained at 30.00, 33.35, 24.14, and 26.84 nm for HAp/Alg/CuO-1, HAp/Alg/CuO-2, HAp/Alg/CuO-3, and HAp/Alg/CuO-4, respectively. FTIR analysis confirmed the presence of the hydroxyl, phosphate, carboxylic, and metal-oxide (Cu–O) bonds. SEM images revealed irregularly shaped, agglomerated particles with an average particle size of 0.416 μm. EDS spectra exhibited calcium, carbon, phosphorus, and oxygen elements. Clindamycin-loaded HAp/Alg/CuO composites were assessed for their antibacterial efficacy against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria. The inhibition zones observed suggest that clindamycin-loaded HAp/Alg/CuO composites hold promise as drug delivery vehicles. Further investigation and development of these composites are warranted, with potential applications in treating specific ailments attributed to S. aureus and E. coli infections, such as osteomyelitis.
The prediction of pH-dependent interaction using micro-dissolution approach in bio-relevant media: Insights from model drug study of lapatinib
Authors: Rajpurohit nithakumari Uttam Singh , Patil Prajakta Harish , Desai Mrunal , Channabasavaiah Jagadish Puralae
Published: April 2024

Understanding the impact of dynamic alterations in gastrointestinal fluid properties and intestinal dissolution of poorly soluble drugs, such as lapatinib, is crucial for predicting drug absorption in vivo. The current study employs a micro-dissolution pH shift model to forecast the dynamic dissolution of lapatinib in buffer and bio-relevant media by application of analytical design of experiments. The utilization of a Box-Behnken design has resulted in a robust analytical method. According to an in vitro micro-dissolving pH shift experiment in United States Pharmacopeia buffers, lapatinib displays a typical weak base pH-dependent solubility, with 15% drug release at pH 1.2 and dropping to 2% at pH 6.5 buffers. In contrast, the solubility of the compound was initially measured to be 0.0127 mg/ ml in fasted state-simulated gastric fluid; however, pH alterations by the addition of fasted state-simulated intestinal fluid 6.5 resulted in a significant increase to 0.0291 mg/ml. The in vitro pH-effect risk for dissolution experiment in bio-relevant media is 0.80, suggesting that the existence of salts in fasted state-simulated intestinal fluid results in the formation of a macroaggregate that is accountable for improved solubility of lapatinib. Thus, using a bio-relevant buffer in a pH shift model may improve this in vitro technique’s predictive ability and aid weakly drug advancement in the intestinal environment.
A dive into natural leads against depression from family Lamiaceae
Authors: Singh Pargat , Kaushik Ujjwal
Published: April 2024

One of the most significant herbal families, the Lamiaceae, has a vast range of plants having biological and therapeutic uses. Due to its curative and preventative qualities, species of the Lamiaceae family have a long history of usage in flavoring, food preservation, and medicine. The family comprising around 236 genera is known for the herbaceous plant species enriched in aromatic compounds. The review focuses on the potential antidepressant properties, active ingredients, and potential mechanisms of action of plant species found in the selected unexplored genus of the Lamiaceae family. The insights emphasized in this review will contribute to the body of knowledge on the unique effects of Lamiaceae plants on depression. It is possible to do more research on the plant species covered under each genus to identify and isolate potentially active substances that may have commercial application in medicinal industry.
Drug delivery to the lymphatic system: The road less travelled
Authors: Rama Annamalai , Govindan Induja , Kailas Anjana A. , Annadurai Thamizharasan , Lewis Shaila Angela , Ranganath Pai Sreedhara , Naha Anup
Published: April 2024

This article explores the physiological and pharmaceutical barriers influencing drug bioavailability for the oral route of administration, as well as the different pharmaceutical technologies and drug delivery systems that have been explored to enhance oral drug absorption. The manuscript also examines the advantages and limitations of drug delivery to the lymphatic system and presents the future directions and challenges associated with this approach. Specifically, the manuscript highlights that drug delivery to the lymphatic system holds promise for improving drug bioavailability and efficacy. It emphasizes the advantages of delivering drugs to the lymphatic system, including enhanced drug solubility, stability, lymphatic transport, and the ability to target specific lymphatic vessels. The manuscript further explores future directions in this field, such as developing novel formulations, targeting specific lymphatic vessels, and combination therapy. However, the manuscript acknowledges significant challenges for the clinical translation of lymphatic drug delivery approaches. Regulatory hurdles, safety concerns, and cost and scalability are vital obstacles to address. The manuscript concludes by emphasizing the importance of addressing these challenges and fostering further research and collaboration to optimize the clinical translation of lymphatic drug delivery.
Experimental evolution for the recovery of growth loss due to genome reduction
Authors: Hitomi Kenya , Ishii Yoichiro , Ying Bei-Wen
Published: April 2024

As the genome encodes the information crucial for cell growth, a sizeable genomic deficiency often causes a significant decrease in growth fitness. Whether and how the decreased growth fitness caused by genome reduction could be compensated by evolution was investigated here. Experimental evolution with an
Escherichia coli
strain carrying a reduced genome was conducted in multiple lineages for approximately 1,000 generations. The growth rate, which was largely declined due to genome reduction, was considerably recovered, associated with the improved carrying capacity. Genome mutations accumulated during evolution were significantly varied across the evolutionary lineages and were randomly localized on the reduced genome. Transcriptome reorganization showed a common evolutionary direction and conserved the chromosomal periodicity, regardless of highly diversified gene categories, regulons, and pathways enriched in the differentially expressed genes. Genome mutations and transcriptome reorganization caused by evolution, which were found to be dissimilar to those caused by genome reduction, must have followed divergent mechanisms in individual evolutionary lineages. Gene network reconstruction successfully identified three gene modules functionally differentiated, which were responsible for the evolutionary changes of the reduced genome in growth fitness, genome mutation, and gene expression, respectively. The diversity in evolutionary approaches improved the growth fitness associated with the homeostatic transcriptome architecture as if the evolutionary compensation for genome reduction was like all roads leading to Rome.
X-ray structure and enzymatic study of a bacterial NADPH oxidase highlight the activation mechanism of eukaryotic NOX
Authors: Petit-Hartlein Isabelle , Vermot Annelise , Thepaut Michel , Humm Anne-Sophie , Dupeux Florine , Dupuy Jerome , Chaptal Vincent , Marquez Jose Antonio , Smith Susan ME , Fieschi Franck
Published: April 2024

NADPH oxidases (NOX) are transmembrane proteins, widely spread in eukaryotes and prokaryotes, that produce reactive oxygen species (ROS). Eukaryotes use the ROS products for innate immune defense and signaling in critical (patho)physiological processes. Despite the recent structures of human NOX isoforms, the activation of electron transfer remains incompletely understood. SpNOX, a homolog from Streptococcus pneumoniae, can serves as a robust model for exploring electron transfers in the NOX family thanks to its constitutive activity. Crystal structures of SpNOX full-length and dehydrogenase (DH) domain constructs are revealed here. The isolated DH domain acts as a flavin reductase, and both constructs use either NADPH or NADH as substrate. Our findings suggest that hydride transfer from NAD(P)H to FAD is the rate-limiting step in electron transfer. We identify significance of F397 in nicotinamide access to flavin isoalloxazine and confirm flavin binding contributions from both DH and Transmembrane (TM) domains. Comparison with related enzymes suggests that distal access to heme may influence the final electron acceptor, while the relative position of DH and TM does not necessarily correlate with activity, contrary to previous suggestions. It rather suggests requirement of an internal rearrangement, within the DH domain, to switch from a resting to an active state. Thus, SpNOX appears to be a good model of active NOX2, which allows us to propose an explanation for NOX2’s requirement for activation.
Merging multi-omics with proteome integral solubility alteration unveils antibiotic mode of action
Authors: Maity Ritwik , Zhang Xuepei , Liberati Francesca Romana , Scribani Rossi Chiara , Cutruzzolá Francesca , Rinaldo Serena , Gaetani Massimiliano , Aínsa José Antonio , Sancho Javier
Published: April 2024

Antimicrobial resistance is responsible for an alarming number of deaths, estimated at 5 million per year. To combat priority pathogens, like Helicobacter pylori, the development of novel therapies is of utmost importance. Understanding the molecular alterations induced by medications is critical for the design of multi-targeting treatments capable of eradicating the infection and mitigating its pathogenicity. However, the application of bulk omics approaches for unraveling drug molecular mechanisms of action is limited by their inability to discriminate between target-specific modifications and off-target effects. This study introduces a multi-omics method to overcome the existing limitation. For the first time, the Proteome Integral Solubility Alteration (PISA) assay is utilized in bacteria in the PISA-Express format to link proteome solubility with different and potentially immediate responses to drug treatment, enabling us the resolution to understand target-specific modifications and off-target effects. This study introduces a comprehensive method for understanding drug mechanisms and optimizing the development of multi-targeting antimicrobial therapies.
Released Bacterial ATP Shapes Local and Systemic Inflammation during Abdominal Sepsis
Authors: Spari Daniel , Schmid Annina , Sanchez-Taltavull Daniel , Murugan Shaira , Keller Keely , Ennaciri Nadia , Salm Lilian , Stroka Deborah , Beldi Guido
Published: April 2024

Sepsis causes millions of deaths per year worldwide and is a current global health priority declared by the WHO. Sepsis-related deaths are a result of dysregulated inflammatory immune responses indicating the need to develop strategies to target inflammation. An important mediator of inflammation is extracellular adenosine triphosphate (ATP) that is released by inflamed host cells and tissues, and also by bacteria in a strain-specific and growth-dependent manner. Here, we investigated the mechanisms by which bacteria release ATP. Using genetic mutant strains of
Escherichia coli
(
E. coli
), we demonstrate that ATP release is dependent on ATP synthase within the inner bacterial membrane. In addition, impaired integrity of the outer bacterial membrane notably contributes to ATP release and is associated with bacterial death. In a mouse model of abdominal sepsis, local effects of bacterial ATP were analysed using a transformed
E. coli
bearing an arabinose-inducible periplasmic apyrase hydrolyzing ATP to be released. Abrogating bacterial ATP release shows that bacterial ATP suppresses local immune responses, resulting in reduced neutrophil counts and impaired survival. In addition, bacterial ATP has systemic effects via its transport in outer membrane vesicles (OMV). ATP-loaded OMV are quickly distributed throughout the body and upregulated expression of genes activating degranulation in neutrophils, potentially contributing to the exacerbation of sepsis severity. This study reveals mechanisms of bacterial ATP release and its local and systemic roles in sepsis pathogenesis.