bluuebunny/crossref_metadata_2025 huggingface dataset:
The secret of production: Commercial value under the condition of obstacle access (legal aspect)
Authors:   Donetsk National University of Economics and Trade named after Mikhail Tugan-Baranovsky, Shirkova Irina V.
Published: October 2024

The new economic system requires new legal solutions to ensure legal protection, which is in demand in modern realities of an intellectual property object, the legal regime of which in both international and domestic legislation has not been properly disclosed. In the scientific literature, there are many conceptions of definitions, but the unity in their understanding has not been achieved. The concept of “secret of production” is contained in many laws around the world, but there is no clear definition. Taking into account the multifaceted nature of the definition of “trade secret”, it is quite possible and expedient from a scientific point of view to analyze individual provisions of this phenomenon, taking into account the legal regulation of the protection and protection of exclusive rights to trade secrets. In the study of the essence of the secret of production, the dialectical method was used, which made it possible to comprehensively study the essence of the subject. Generalization of the existing definitions, and the legal framework made it possible to highlight the characteristic features of the studied category: information relates to the scientific and technical sphere, and is also focused on ways of carrying out professional activities; actual or potential commercial value; unknown information to third parties; lack of free access to information; taking reasonable steps to maintain confidentiality; subjects — an individual, an individual entrepreneur, and a legal entity with the exclusive right to use the secret of production; the period of validity of the exclusive right is not limited by law, it is valid as long as the confidentiality of information is ensured. Methods of disposing of exclusive rights to production secrets have been systematized. The necessity of changing the legislation governing the protection of the production secret (know-how) has been substantiated.
Sufficiency of evidence in court decisions in criminal cases: Particular problems
Authors:   St. Petersburg State University, Sidorova Nataliia A. , Vasilyev Ilia A. ,   St. Petersburg State University
Published: October 2024

The article analyzes problems of assessing evidence in criminal cases, in particular, the use by courts of such a criterion when assessing the sufficiency of evidence. In the absence of this criterion, it is impossible to talk about compliance with the requirements for the sentence and, as a consequence, about the legality of the latter. However, the law does not contain objective criteria for assessing a sufficient body of evidence to make a decision in a case. The concepts of standards of proof and standards of proof in a case developed in the doctrine of criminal procedure are currently only theoretical constructs. The article analyzes the positions of the courts of appeal, cassation and supervisory instances in assessing evidence. The categories under consideration — the totality of evidence, the limits of proof and the sufficiency of evidence — are often used in judicial decisions of courts of various instances. Judicial acts containing conclusions about evidence, the totality of which is recognized as sufficient to establish the guilt of the defendant, often indicate evidence of questionable quality, drawn up and obtained in violation of the Code of Criminal Procedure of the Russian Federation, containing factual errors. The use by courts of standard formulations about the “sufficiency of the totality of evidence”, which is present in all the studied cases, and they are characterized to a greater extent by an acceptable quantitative level than a qualitative component, is probably due to the fact that in the current criminal procedural legislation there is no necessary definition of the concept of “sufficiency”. And as a result, a significant part of judicial acts contain wording that is of a standard nature, indicating the need to confirm the court’s conclusions “with the totality of evidence examined by the court”.
The system of Chinese legal sources from the perspective of the platform economy legal regulation
Authors:   St. Petersburg State University, Alekseenko Aleksandr , Malysheva Natalia I. ,   St. Petersburg State University
Published: October 2024

Despite intensification cooperation with China, Russian legal science doesn’t provide comprehensive study of Chinese laws and regulations concerning entrepreneurial activity including e-commerce. Analysis of the concept “source of law” allows to demine a fairly wide range of Chinese legal sources. Basing on the analysis of the laws of the People’s Republic of China, regulations of the State Council, notices of the People’s Bank of China, notifications, notices of measures, regulations, letters from various Chinese public bodies and local regulations, this paper examines the sources (forms) of legal regulation of the platform economy in China from theoretical perspective. The purpose of this article is to reconstruct the system of sources (forms) of law in the sphere of the Chinese platform economy, to qualify sources and establish hierarchical relationships between them in order to identify contradictions and ways to overcome them. The paper concludes that in China there are no clear criteria for distinguishing between subordinate legislation and acts of interpretation, also legal provisions sometimes may be included in interpretational documents. Official replies and letters from government agencies in China like legal regulations may impose new responsibilities on lower-level public bodies. The paper concludes that China doesn’t have definite border between notifications and notices issued by ministries and departments. Authors also stress the discussion on the legal nature of judicial clarifications and guiding court cases of the Supreme People’s Court of the People’s Republic of China.
Restrictive covenants in agreements between entrepreneurs and their employees under the law of foreign countries. Part two: Germany, France, Japan, China and the Eurasian Economic Union
Authors:   University of Tyumen, Chukreyev Andrey A.
Published: October 2024

This review article is devoted to restrictive covenants, which are widely used in contracts between entrepreneurs and their employees in many countries. In Russia, these covenants are not supported by the courts. It is believed that such restrictions are contrary to the constitutional and other norms of Russian law. The purpose of this study is to analyze the foundations of legal regulation in a number of countries of such restrictive covenants as non-competition agreements, non-solicitation agreements, non-dealing agreements and non-disclosure agreements. This analysis is necessary for a reasonable answer to the question of the advisability of recognizing in Russia the legality of such agreements. The first part of this article provides an overview of the law on non-competition and other similar covenants of the United Kingdom and the United States, in the second part — Germany, France, Japan, China and the Eurasian Economic Union. In jurisdictions where non-competition agreements and other similar restrictive covenants are not prohibited, the “rule of reason” acts as a legal mechanism for balancing the competing interests of employers, employees and public interests. This rule allows the courts in each specific dispute to assess the specified conditions for their compliance with the protected business interest of the employer and other criteria. The conclusion is made about the advisability of legalizing agreements on non-competition, non-engagement and non-entrepreneurship in Russia, taking into account the positive foreign experience of legal regulation in this area. In this regard, it will be necessary to legislate in Russian law an analogue of the rule of reason.
Legal Framework for Impact Financing in the Digital Economy: What the Future Looks Like for the BRICS+ Countries
Authors: Belitskaya A. , Kharitonova Yu.
Published: October 2024

The article is devoted to the analysis of the legal regulation of the process of introducing FinTech in the sphere of impact finance within the context of digital technologies in the newly expanded BRICS bloc. This is a crucial step in order to be able to meet the challenges of the new global digital economy and cooperate in achieving common goals. The authors come to the conclusion that although the BRICS countries are geographically located on different continents, the states that decided to form this organization share a number of key features. Firstly, the governmental role in the digital transformation of all BRICS countries is significantly greater in comparison to the Western countries. Secondly, because not all BRICS countries have developed economies, the BRICS member states, despite their strong interest in digitalization of their countries, do not always have the capacity to finance such projects from their own national budgets, which highlights the important role of the BRICS New Development Bank in the process of digitalization of the BRICS economies. Thirdly, cooperation among the BRICS countries, through their participation in the New Development Bank in the digital realm, can significantly contribute to fostering the economic growth of each country within the integration. Since the greatest effect of digital technology penetration is achieved when starting from the lowest level, harmonization of approaches in the BRICS countries and new member countries of the bloc will most likely have a synergistic effect.
Legal Support of Artificial Intelligence in Countering Anti-Money Laundering and Terrorism Financing Regimes in the BRICS Plus Countries
Authors: Aksenova M.
Published: October 2024

The increasing integration of artificial intelligence technologies into the financial structures of the BRICS Plus countries (comprising the original member countries of Brazil, Russia, India, China, and South Africa as well as the four new member countries of Egypt, Ethiopia, Iran, and the United Arab Emirates) presents both opportunities and challenges in combating economic crimes, which include money laundering and terrorism financing. This article explores the complex regulatory landscape that governs the application of artificial intelligence in these efforts. It examines how artificial intelligence can enhance the performance of anti-money laundering and counter-terrorism financing frameworks by enabling the evaluation of massive datasets, the identification of anomalous transaction patterns, and the automation of compliance procedures. Simultaneously, the article addresses the highly challenging situations that arise when using artificial intelligence. For instance, these technologies can make it difficult to understand the fluctuation of illicit price ranges, thereby complicating efforts to determine their origins and destinations. Through a comparative analysis of the frameworks throughout the BRICS Plus countries, this research highlights the varying levels of regulatory readiness of these frameworks and proposes pathways for harmonizing artificial intelligence-driven economic security measures. The overarching goal of an artificial intelligence model is to enhance both the effectiveness and the integrity of the financial sectors in the BRICS Plus consortium, necessitating a collaborative approach to combating financial crimes in an increasing number of digital economies across the world.
A importância do aleitamento materno exclusivo nos 6 primeiros meses de vida
Authors: Bazilio Graciele de Fátima , Souza Alessandra da Silva , Lima Thainá Oliveira , Silva Eliara Adelino da , Silva Jannaína Sther Leite Godinho da
Published: October 2024

Introdução: Apesar de a prevalência da amamentação no Brasil ter crescido nas últimas décadas, ainda há muito que se realizar para que se possa atingir a recomendação da Organização Mundial da Saúde (OMS), de AME nos primeiros seis meses de vida da criança e manutenção da amamentação até o segundo ano de vida ou mais. O objetivo geral do trabalho é conhecer os benefícios do aleitamento materno exclusivo até os 6 meses de idade da vida da criança, passando pelos benefícios fisiológicos e de desenvolvimento. Materiais e Métodos: Tratou-se de um estudo qualitativo, exploratório descritivo que foi realizado através de uma revisão integrativa de literatura. Resultados: Foram selecionados para esta pesquisa 7 artigos compondo o conteúdo do presente estudo. Os 7 estudos foram lidos integralmente e avaliados com o objetivo de extrair informações para a coleta de dados e os resultados foram submetidos á uma análise descritiva, uma vez que as publicações obtidas apresentaram desfechos distintos. Conclusão: Portanto, diante das evidências científicas apresentas, é necessário que ocorra maiores estratégias eficazes de promoção do aleitamento materno exclusivo, com foco na conscientização das mães, suporte dos profissionais de saúde e superação de desafios que possam surgir, contribuindo assim para a saúde global e bem-estar a longo prazo das crianças e suas mães. Além disso, é importante que o enfermeiro tenha conhecimento sobre os riscos da introdução de alimentos ultraprocessados precocemente na vida dessas crianças e as consequências para o crescimento e desenvolvimento do lactente.
Palavras-Chave: Enfermagem; Aleitamento Materno; Aleitamento Materno Exclusivo; Assistência de Enfermagem.
Medicamentos de uso off-label para terapia subcutânea: uma revisão sistemática
Authors: Santos Fernanda Maria Ramos dos , De Paula Danielle Galdino , Antunes Alice Andrade , Barbosa Maria Fernanda
Published: October 2024

Trata-se de artigo de revisão sistemática que aborda tema relevante para a área da saúde relacionado ao uso da via subcutânea para administração de medicamentos a pacientes de cuidados paliativos. Com a progressão da doença, para tais pacientes, muitas vezes o uso da via endovenosa e até mesmo da via oral, acabam contraindicados. Contudo o uso da via subcutânea constitui-se, na maioria das vezes, uma prática off-label. Consequentemente, com vistas a garantir a eficácia terapêutica e a segurança do paciente, o levantamento de evidências atualizadas para a implementação desta estratégia assistencial no ambiente hospitalar, é fundamental. Desta forma este artigo representa o primeiro passo necessário para a futura elaboração de um guia validado de medicamentos para administração off-label pela via subcutânea, fruto de Mestrado Profissional em curso. Objetivo: O estudo teve como objetivo identificar e analisar evidências sobre medicamentos administrados por via subcutânea para hidratação e controle de dor, náuseas, vômitos e dispneia. Método: Realizou-se uma revisão sistemática da literatura entre 2013 e 2023, utilizando bases de dados como Pubmed, LiLACS, SCIELO e Google. Resultados: Foram analisados qualitativamente 22 artigos científicos e 2 guias de instituições renomadas em Cuidados Paliativos. A administração off-label subcutânea foi considerada segura e eficaz em 77,3% dos estudos, apesar da baixa robustez das evidências. Conclusões: O estudo permitiu a identificação dos medicamentos mais utilizados em cuidados paliativos que são passíveis de administração off-label por via subcutânea. No entanto, destaca-se a necessidade de estabelecimentos de critérios rigorosos para sua utilização devido à precaução indicada pelo nível de evidência, enfatizando a importância de estudos mais consistentes nessa área.
Importância da Metodologia Lean Healthcare para a Qualidade da Assistência nas Emergências
Authors: Santos Juliana Nogueira dos , Carvalho Camuzi Ranieri , Cordeiro Benedito Carlos
Published: October 2024

A alta demanda por serviços de atendimento de urgência e emergência e as deficiências nos processos de trabalho podem contribuir para a superlotação das emergências. A metodologia Lean Healthcare permite mapear a cadeia de valor, identificar o valor dos processos e destacar as atividades que não o geram, através da adoção de recursos pelas organizações para atuarem diretamente no que agrega valor na percepção do usuário. O objetivo deste estudo foi avaliar se a utilização da metodologia Lean Healthcare poderia ser uma estratégia para promover a qualidade no setor de urgência e emergência das unidades da Rede de Urgência e Emergência de um município do Região Metropolitana do Rio de Janeiro. Os dados foram coletados por meio de questionário estruturado aplicado antes e após a Oficina Lean Healthcare, utilizando Team-Based Learning, no qual os profissionais identificaram os principais nós críticos nos processos de trabalho. Ao analisar os resultados foi possível observar que os líderes já possuíam um nível de conhecimento sobre Lean Healthcare, sendo aprofundado após a oficina. Os principais nós críticos identificados foram: falta de compreensão da metodologia Lean Healthcare pelas equipes, fraca gestão de recursos, sobrecarga de trabalho e falta de integração entre os setores. Portanto, pode-se concluir que a metodologia Lean Healthcare é uma ferramenta eficaz para promover a qualidade na saúde devido à sua estratégia de identificar nós críticos nos diferentes processos de trabalho.
Astaxanthin Is a Novel Candidate for Glioblastoma Treatment? A Review
Authors: Rezaee Arian , Radmanesh Mehrsa , Asghari Atena , Nazari Ahmad , Shahidi Amir Abbas , Chahardehi Amir Modarresi , Arefnezhad Reza , Farkhondeh Tahreh , Saminin Mohammad , Samarghandian Saeed
Published: October 2024

Glioblastoma (GBM) is a malignant primary brain tumor with a poor prognosis
and high recurrence rates. At present, the current treatments available for GBM patients
can only prolong their overall survival and cannot provide a complete cure. Discovering
an effective therapy against the disease is a challenge due to its recurrence and
resistance to common available treatments for GBM. Several natural products have been
documented to possess the potential to function as anticancer agents through diverse
mechanisms. Astaxanthin (AXT) is an orange-red pigment that is a natural lipophilic
and xanthophyll carotenoid derived mostly from microalgae. Numerous studies have examined
that AXT impacts GBM cells in laboratory settings and animal models. This review
aims to provide the latest information about the potential of astaxanthin as a novel
therapeutic option for GBM. AXT has been targeted more on reactive oxygen species
(ROS), and suppressed tumor growth in vitro and in vivo conditions. The available data
suggests that AXT might serve as a key component in the development of innovative
cancer therapies, especially for glioblastoma.
Role of Ferroptosis in ALD: Focusing on Hepcidin and Besides Hepcidin
Authors: Chen Leijie , Zhou Hejun , Cheng Zongyong , Liu Deliang , Tan Yuyong
Published: October 2024

Ascending incidence and poor outcomes make Alcoholic Liver Disease
(ALD) a considerable public health concern. This review concluded the iron metabolism
under physiology conditions and alcohol disturbance (leading to ferroptosis in ALD)
and summarized the novel treatment, diagnosis, and prognosis of ferroptosis for ALD.
ALD is characterized by alcohol-induced chronic metabolism disorder, peroxidation damage,
and dysfunction of the anti-oxidant system. Current animal experiments and clinical
studies identified ferroptosis as a new form of regulated cell death involved in ALD.
One strong evidence is that the key iron regulatory hormone, hepcidin, is downgraded in
ALD through NF-κB/IL-6/STAT3, BMP/SMAD, and Jak/STAT3 pathways, which
would impair iron hemostasis and induce ferroptosis in ALD. Also, imbalance
metabolism and other pathological responses in ALD induce and regulate ferroptosis,
which proves ferroptosis participates in the pathophysiology of ALD via oxidative
stress, steatosis, and fibrosis. Inhibition of ferroptosis via regulating hepcidin expression
and metabolism impairment may provide new therapies for ALD.
Astaxanthin Alleviates Chronic Prostatitis via the ERK1/2 Signaling Pathway: Evidence from Network Pharmacology and Experimental Validation
Authors: Liu Yifu , Huang Liang , Zhang Zhicheng , Zhu Qiqi , Xi Ping , Sun Ting , Gong Binbin
Published: October 2024

Background:

Astaxanthin (AST) has been widely recognized for its therapeutic potential
in chronic inflammatory ailments. This study investigates the therapeutic efficacy and underlying
mechanisms of AST in the management of chronic prostatitis (CP).

Methods:

Male Sprague-Dawley (SD) rats were randomly divided into control, complete
Freund's adjuvant (CFA), and CFA + AST groups. CFA was used to induce the CP model, and
saline was used for the control group. Inflammation of the prostate was detected 28 days after
oral administration of AST. qRT-PCR and ELISA were used to detect pro-inflammatory factors
in RWPE-1 and WPMY-1 cells. Potential targets of AST for CP were explored by network
pharmacology, and related proteins were detected by Western blotting.

objective:

This study investigates the therapeutic efficacy and underlying mechanisms of AST in the management of chronic prostatitis (CP).

Results:

Oral administration of AST alleviated the increase in prostate stroma and reduced inflammatory
cell infiltration in CP rats. The IC50 of AST-treated RWPE-1 and WPMY-1 cells for
48 h were 171 and 212.1 μM, respectively. AST pretreatment reduced IL-6 and IL-8 expression
in these cells. PPI network, GO, and KEGG enrichment analyses suggested that the antiinflammatory
effect of AST was associated with the ERK1/2 pathway. Western blotting showed
that AST inhibited ERK1/2 phosphorylation. In addition, AST and ERK1/2 pathway inhibitors
(U0126) synergistically inhibited LPS-induced inflammation in prostate cells.

Conclusion:

Our study identified the potential of AST in the treatment of CP. However, subsequent
randomized controlled trials are needed to validate its clinical efficacy.
Anthelmintic Activity of Carica papaya Leaf Extracts: Insights from In Vitro and In Silico Investigations
Authors: Alhaiqi Nawal S. , Afifi Sherine M. , Mahyoub Jazem A. , Abdel-Gaber Rewaida A. , Delic Denis , Dkhil Mohamed A.
Published: October 2024

Introduction:

Helminthiasis remains a major global health concern. Exploring natural
alternatives due to drug resistance and synthetic drug side effects has become increasingly urgent.

Method:

This study investigates the anthelmintic potential of Carica papaya leaf extracts
(CPLE) against Allolobophora caliginosa, along with elucidating the underlying structural alterations
and molecular interactions. Carica papaya underwent methanolic extraction. Gas chromatography-
mass spectrometry analysis revealed 11 active phytochemical compounds within
CPLE. The anthelmintic activity was evaluated against A. caliginosa, with CPLE demonstrating
efficacy comparable to albendazole. Light microscopy and scanning electron microscopy depicted
structural modifications in worms exposed to CPLE, characterized by reduced size, uniform
shrinkage, and increased cuticle thickness.

Result:

Molecular docking studies with proteins Ascaris lumbricoides β-tubulin and Trichuris
trichiura β-tubulin revealed potential binding interactions of CPLE compounds, notably Hexadecanoic
acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester, and Albendazole oxide.

Conclusión:

These findings suggest the anthelmintic efficacy of CPLE and provide insights into
its mode of action at the molecular level.
Bridging the GAP: Probiotic Douches Redefining the Feminine Hygiene
Authors: Kumar Akash , Hussain Sadique , Srivastava Nitya , Singh Gurvinder , Gulati Monica , Kumar Rajesh
Published: October 2024

Vaginal douching is a centuries-old practice which is still in use, especially among
adolescents. "Probiotic douches" are the vaginal douches that are formulated with probiotics and
are intended to restore or maintain the vaginal microbiome balance. Probiotic douches are a new
type of feminine hygiene product that claims to promote a balanced vaginal microbiome and
improve overall well-being. However, the evidence supporting the use of probiotics for vaginal
health is limited because of the variability in probiotic strains and dosages studied, and the lack
of more comprehensive, long-term clinical trials. Most of the existing scientific literature on
probiotics focuses on oral probiotic supplements and vaginal probiotic suppositories. Some potential
benefits of probiotic douches include restoring a balanced vaginal microbiota, preventing,
or managing infections, supporting local immune function, reducing odor and discharge, and
enhancing overall vaginal comfort. However, it is important to note that these benefits have not
been definitively proven and remain a subject of ongoing research. There are also potential risks
associated with their use including disruption of the natural vaginal ecosystem by introducing
foreign substances, risk of infection, and stability issues with the formulation that may lead to
negative consequences. This review attempts to comprehend the critical need for robust scientific
research to guide the safe and effective incorporation of probiotic douches into modern feminine
hygiene practices, revolutionizing women's health, and well-being.
Potentiation of Tumor Hallmarks by the Loss of GULO, a Vitamin C Biosynthesis Gene in Humans
Authors: Sekar Gopinath , Bahot Anjali , Bansode Mahima , Phadnis Anushka , Sarode Sachin C , Sharma Nilesh Kumar
Published: October 2024

Vitamin C plays a significant role in various physiological functions. Humans
depend on external sources of vitamin C due to the loss of the L-gulono-γ-lactone
oxidase (GULO) gene that contributes to the synthesis of vitamin C. During the
evolutionary loss of the GULO gene, physical, chemical, and biological factors were
different from the present environmental settings. Besides the evolutionary genetic
loss of the GULO gene, there is a gap in the insightful discussion on the potential
implications of the non-functional GULO gene towards the predisposition of humans to
cancer that faces hostile and carcinogenic environments. Various methods by which
vitamin C modulates cellular processes related to cancer, including DNA repair,
epigenetic changes, and redox balance, are discussed. Furthermore, we present
experimental and clinical evidence indicating that vitamin C deficiency promotes tumor
growth, metastasis, and therapy resistance, emphasizing its potential as a cancer
phenotypic modulator. Therapeutic implications of restoring vitamin C levels in cancer
treatment range from improving the efficacy of conventional medicines to exploiting
metabolic vulnerabilities in tumors. The relevance of assessing vitamin C status in
cancer patients and the basis for additional research into vitamin C supplementation
as an adjuvant therapy is emphasized. This paper presents a comprehensive overview
of the implications associated with the functional deficiency of the GULO gene in
human subjects exhibiting diverse tumor hallmarks, encompassing ECM remodeling,
hypoxia, epigenetic reprogramming, oxidative stress, and drug responsiveness.
Alleviation of Tumor Invasion by the Development of Natural Polymerbased Low-risk Chemotherapeutic Systems – review on the Malignant
Carcinoma Treatments
Authors: Natarajan Vignesh
Published: October 2024

Introduction/Objective:

The spread of tumors (48% in men and 51% in women), as well
as the protection of malignant tumors by stromal cells and complex blood vessels, pose significant
challenges to drug delivery to tumors. Modern chemotherapy, on the other hand, addresses tumor
growth suppression by at least 60% through versatile formulation systems and numerous modifications
to drug delivery systems. The renewable and naturally occurring polymers present invariably in
all living cells form the fundamental foundation for most anticancer drug development. The review
aims to discuss in detail the preparations of polysaccharide, lipid, and protein-based drug-loading
vehicles for the targeted delivery of prominent anticancer drugs. It also provides an explanation of
drug distribution in blood (cumulative releases of nearly 80% drug) and drug accumulation at tumor
sites (1–5 mg/kg) due to enhanced permeability and retention (EPR).

Methods:

Specific delivery examples for treating colorectal and breast carcinomas have been presented
to distinguish the varied drug administration, bioavailability, and tumor internalization mechanisms
between sugar, fatty acid, and amino acid polymers. Current therapy possibilities based on
cutting-edge literature are provided, along with drug delivery systems tailored to tumor location and
invasive properties.

Results:

The unique combinations of the three natural polymers provide unparalleled solutions to
minimize the toxicity (<20% drug release) of the chemotherapeutic drugs on normal tissues. Moreover,
the development of a consolidated drug delivery system has contributed to a substantial reduction
(dose reduction from 10.43 μM to 1.9 μM) in the undesirable consequences of higher dosages of
chemotherapeutic drugs.

Conclusion:

The review extensively covers safe chemotherapeutic systems with significant advantages
(tumor volume shrinkage of 4T1 cells from 1000 mm3 to 200 mm3) in clinical applications
of carcinoma treatments using natural polymers.
Identification of PANoptosis Subtypes to Assess the Prognosis and Immune Microenvironment of Lung Adenocarcinoma Patients: A Bioinformatics Combined Machine Learning Study
Authors: Zhou Xiaofeng , Wang Bolin , Wu Di , Gao Lu , Wan Zhihua , Wu Ruifeng
Published: October 2024

Background:

PANoptosis, a novelty mechanism of cell death involving crosstalk between apoptosis, pyroptosis, and necroptosis, is strongly associated with tumor cell death and immunotherapy efficacy. However, its relevance in lung adenocarcinoma (LUAD) remains to be elucidated.

Methods:

In this study, we acquired 18 PANoptosis-related differentially expressed gene (PRDEG) of LUAD. Based on these genes, LUAD samples were identified with different sub-types by unsupervised clustering. Next, we compared the differences between the subtypes, including clinical features, immune microenvironment, and potentially sensitive drugs. Further-more, we used machine learning to identify hub prognostic PRDEGs, construct a risk score, and validate it on other external datasets. We incorporated the patient's clinical information and risk score into the proportional hazards model and lasso-cox models to find key prognostic features and constructed five prognostic models. The best model was identified via the area under the curve and validated on an external dataset.

Results:

LUAD patients were divided into two clusters named C1 and C2, respectively. The C2 cluster exhibited shorter survival time, more advanced tumor stage, higher suppressive immune cell scores, such as dendritic cells, and higher expression of inhibitory immune checkpoints, such as LAG3 and CD86. TIMP1, CAV1, and CD69 were recognized as key prognostic factors, and risk scores predicted survival with significant differences in the external validation set. Risk score and N-stage were identified as critical prognostic features. The Coxph model outper-formed other machine learning clinical models. The 1-, 3-, and 5-year time-ROCs in the exter-nal validation set were 0.55, 0.59, and 0.60, respectively.

Conclusion:

We demonstrated the potential of PANoptosis-based molecular clustering and prognostic features in predicting the survival of patients with LUAD as well as the tumor mi-croenvironment.
Computational Studies in Dermo-cosmetics: In silico Discovery of Therapeutic Agents Targeting a Variety of Proteins for Skin Diseases
Authors: Bouamri Lamiae El , Bouachrine Mohammed , Chtita Samir
Published: October 2024

Healthy skin is essential for balanced health. Currently, skin diseases are considered a
major global health issue, impacting individuals of all ages. Skin conditions can vary broadly,
ranging from common issues like acne and eczema to more serious diseases such as psoriasis,
melanoma, and other types of skin cancer. In recent years, computational methods have appeared
as powerful tools for explaining the lurking mechanisms of skin diseases and the advancement of
the discovery regarding updated therapeutics. This review spotlights the notable researches that
have been performed in using computational approaches such as virtual screening, molecular
modelling, and molecular dynamics simulations to discover potential treatments for dermatological
conditions such as eczema, psoriasis, acne vulgaris, skin cancer, and tyrosinase-related disorders.
Moreover, using in silico methods, researchers have explored the molecular interactions between
cosmetic actives and skin targets, providing insights into the binding affinities, stability, and
efficacy of these compounds. This computational exploration allows the identification of potential
off-target effects and toxicity profiles, ensuring that only the most promising candidates proceed to
clinical testing. In addition, the use of molecular dynamics simulations helps to understand conformational
changes and interaction dynamics over time, further refining the selection of effective
cosmetic actives. Overall, the integration of computational chemistry into dermo-cosmetic research
has immense potential to accelerate the discovery and development of innovative treatments
to improve skin health and address dermatological concerns.
Determination of FGFR1 Functions in Cytarabine Treatment of Acute Myeloid Leukemia Through Bioinformatics Analysis
Authors: Misir Sema , Yaman Serap Ozer , Aykac Okan , Akidan Osman , Merde Irem Bozbey , Hepokur Ceylan
Published: October 2024

Aim:

Among the most prevalent subtypes of acute leukemia is acute myeloid leukemia
(LAML). Consequently, it is essential to understand the molecular causes of LAML and find its
predictive and diagnostic biomarkers. The aim of this study is to determine the molecular functions
of fibroblast growth factor receptor 1(FGFR1) involved in LAML pathogenesis and its potential
therapeutic effect for AML treatment.

Methods:

The molecular docking interaction of the Cytarabine with its target FGFR1 was examined.
The Gene Expression Profiling Interactive Analysis, version 2 (GEPIA2), and UALCAN
tools database were used to obtain the LAML gene expression datasets. Gene functional annotation
was performed to investigate the DEGs' possible role. Using the Interactive Gene database retrieval
tool (STRING) and a few chosen hub modules from the GeneMANIA database, the protein-
protein interaction (PPI) network were constructed. A survival analysis was performed on the
effects of hub genes on the overall survival of LAML patients.

Results:

As a result of docking, a strong interaction was observed between cytarabine and
FGFR1. It has been discovered that cytarabine can reverse FGFR1 expression. The survival study
results showed an association between the prognosis of AML patients and one of the central
genes, FGFR1.

Conclusion:

The expression profile and functions of FGFR1 were determined in LAML patients.
It has been shown that FGFR1 can be a viable therapeutic target for LAML and a possible biomarker
for diagnosis.
Bakuchiol and their Derivatives: Unveiling its Chemistry, SAR, Pharmacological Marvels and Therapeutic Odyssey
Authors: Chopra Bhawna , Dhiman Simran , Dhingra Ashwani , Jain Akash , Chaudhary Jasmine , Dua Jagdeep Singh , Prasad Deo Nandan
Published: October 2024

Bakuchiol, a meroterpene natural product found in various plants, exhibits diverse biological
activities, notably anticancer properties. Researchers have synthesized numerous analogs
targeting different positions, such as alcoholic OH, ethenyl, and isopropylidene groups within
bakuchiol, aiming to enlighten potent therapeutic agents with enhanced pharmaceutical characteristics.
The review aims to focus on the extensive potential of the bioactive molecule, bakuchiol
describing SAR that may lead to the development of a variety of bakuchiol derivatives. Literature
survey has been carried out to determine the potential of bakuchiol and its derivatives. This review
comprehensively outlines the biosynthesis, isolation, patent, and clinical studies of bakuchiol,
and pharmacological potential of bakuchiol derivatives documented to date. Additionally, it
explores the structure-activity relationships observed in its derivatives. Collectively, findings
from various studies underscore the significant potential of bakuchiol and its derivatives in the
development of potent anticancer and other therapeutic agents. Ultimately, this review serves as a
valuable resource for researchers interested in both the chemistry and biology of bakuchiol, offering
insights into its multifaceted applications and paving the way for further exploration in this
field.
Cucurbitacin-E; Curvularia lunata Secondary Metabolite as a BRCA 1 and 2 Regulator in Mice Associated Breast Cancer
Authors: Abd El-Mongy Mahmoud , Hussein Mohammed Abdalla , EL-Sayed Nooran T. , Salah Ahmed , Roshdy Tamer
Published: October 2024

Background:

Cucurbitacin-induced apoptosis and inhibition of cell growth can render
several cancers ineffective. The microbial transformation of cucurbitacin-E-glucoside to cucurbitacin-
E was carried out by Curvularia lunata (NRRL 2178). Moreover, in vitro anticancer activity
against the MCF-7 cell line as well as in vivo anticancer activity against dimethylbenz (a)
anthracene (DMBA)-induced breast cancer in mice using cucurbitacin-E was evaluated.

Methods:

The cucurbitacin-E-glucoside was biotransformed by Curvularia lunata to cucurbitacin-
E, and the isolated compound was tested in vitro against the MCF-7 cell line, and its IC50 was
calculated. LD50 of cucurbitacin-E was estimated in mice, and its protective activity against
DMBA-induced cancer in mice was studied. Breast cancer induction was done by a single-dose
subcutaneous administration of DMBA (50 mg). Plasma ALT, AST, ALP, and LDH, as well as
GSH, SOD, GPx, MDA, TNF-α, IL-6, and tumor suppressor P53 assays, were used to assess cucurbitacin-
E's capacity to protect the liver and breast against DMBA-induced toxicity. Moreover,
by assessing the gene expression of tumor suppressor genes (BRCA 1 and 2) and conducting histopathological
analysis, the suppressive effect of cucurbitacin-E was examined.

Results:

The IC50 value of cucurbitacin-E against MCF-7 cell lines equals 72.15 ± 0.64 μg/ml.
LD50 of cucurbitacin-E given orally in adult mice is equal to 1200 mg/kg b.w. The levels of
plasma ALT, AST, ALP, and LDH were decreased significantly in DMBA-treated mice when
administered with cucurbitacin-E at 1/50 LD50 (24 mg/kg/b.w.) and 1/20 LD50 (60 mg/kg/b.w.).
In breast tissue, the levels of GSH, SOD, GPx, and P53 were significantly increased, as were decreased
levels of TNF-α, IL-6, P53, and MDA. Conversely, there was a downregulation in the
mRNA expression levels of BRCA1 and BRCA2. The histopathological analysis revealed that
cucurbitacin-E management improved the tissue architecture of breast tumors.

Conclusions:

These findings demonstrate the ability of cucurbitacin-E to inhibit cancer cells in
the rat breast by controlling oxidative stress and inflammatory biomarkers, as well as downregulating
the mRNA expression levels of BRCA1 and BRCA2.
Design, Synthesis, and Study of Novel Memantine Schiff Base Derivatives Against Targeted Enzymes in Alzheimer’s Disease
Authors: K Girija , E Logesh , P Sowmiya , Krishnamurthy Sairam , T.A Gajendra
Published: October 2024

Introduction:

According to WHO, Alzheimer’s disease was estimated at 74.4 million
cases in 2023, which will increase by 152.8 million cases in 2050. The therapeutic options available
in the market for the treatment of AD are only capable of reducing the symptoms of dementia
but not preventing progressive degeneration. Memantine is a non-competitive NMDAR antagonist
used for the treatment of patients with moderate-to-severe AD, but it has a high toxicity profile.
To counter this, the Memantine Schiff base derivatives were designed as simple and lowtoxicity
compounds.

Materials and Methods:

Molecular docking was performed against the targeted enzymes Acetylcholinesterase
and Butyrylcholinesterase using AUTODOCK 1.5.7 software. A series of novel
Memantine derivatives of Schiff base were synthesized by condensing Memantine with various
aryl aldehydes and screened for their invitro-cholinesterase inhibitory activity towards Acetylcholinesterase
(AChE) and Butyrylcholinesterase (BChE) by Ellman’s method.

Results and Discussion:

Among the designed compounds, compounds LMV and LMC showed
maximum binding scores of -10.35 kcal/mol and -10.12 kcal/mol, respectively, than the standard
Donepezil (-8.78 kcal/mol) against Acetylcholinesterase. The compounds LMONB and LMDMB
produced significant binding scores of -9.31 kcal/mol and -9.11 kcal/mol, respectively, compared
to the standard Donepezil (-7.57 kcal/mol) against Butyrylcholinesterase. Also, compounds LMV
(30.9 ± 2.13 μM) and LMDMB (13.51 ± 1.12 μM) showed potent inhibitory activity against the
AChE and BChE. These compounds possess drug-like characteristics and are also capable of
crossing the Blood Brain Barrier (BBB).

Conclusion:

The studied compounds LMV and LMDMB, being non-toxic, obey Lipinski’s rule
of 5 and are potential inhibitors against targeted enzymes, which may be promising clinical candidates
for treating Alzheimer’s disease.
A Method to Determine Metoclopramide Hydrochloride in Oral Dosage Forms by Micellar Liquid Chromatography
Authors: García Ferrer Daniel , Peris-Vicente Juan , Durgbanshi Abhilasha , Bose Devashish , Carda-Broch Samuel
Published: October 2024

Background:

Metoclopramide is a widely prescribed antiemetic drug. Its analysis in
pharmaceutical formulations often involves procedures using high amounts of toxic chemicals.

Objective:

A method based on micellar liquid chromatography to determine metoclopramide hydrochloride
in several oral dosage forms has been developed.

Methods:

The drug was resolved from matrix compounds within 6 min using a C18 column with
isocratic elution at 1 mL/min utilizing a solution of 0.10 mol/L sodium dodecyl sulfate – 6 % 1-
pentanol phosphate buffered at pH 7 as mobile phase, and detection by absorbance at 210 nm. Samples
were dissolved or diluted in the mobile phase and directly injected; thus, only one solution had
to be prepared for the entire procedure. Besides, it contained mainly harmless chemicals and a minimal
amount of organic solvent. Results The procedure was validated by the International Council of
Harmonization guidelines and the results were: specificity, calibration range (0.5 – 5.0 mg/L), linearity
(r2 > 0.9990), trueness (98.1 – 100.3 %), precision (< 0.7%), robustness, carry-over effect, and
system suitability. It was used to analyze commercial samples. Otherwise, it was found the influence
of the surfactant on elution strength was nearly three times stronger than that of 1-pentanol.

Conclusion:

The procedure was reliable, easy-to-conduct, safe, eco-friendly, short-time, widely
available and highly sample-throughput, and then useful for routine analysis of metoclopramidebased
dosage forms in pharmaceutical quality control.
Carbon-based Nanocomposite Materials for Electrochemical Monitoring of Cadmium Ions
Authors: Singh Manorama , Patel Dev Kumari , Bhardiya Smita R. , Kumar Rahul
Published: October 2024

In the present era of science and technology, cadmium poisoning in humans is reported
from several parts of the world and now it is a global health problem.

Accumulation of cadmium in human organs and tissues, such as the liver, kidney, etc., leads to carcinogenic
effects and toxicity to the organ system. Therefore, several efforts are being made to develop
a monitoring system for cadmium metal ions in the environment.

This review aimed to summarise the different carbon-composite materials-based electrochemical
sensors reported to date for cadmium ions detection.

The first section of this review provides a brief discussion on the source and harmful effects of cadmium
ions, and the rest part includes different carbon (graphite, graphene, graphene oxide, carbon
nanotubes, etc.)-based composite nanomaterials reported to date for the electrochemical detection of
cadmium ions in different analytes.

Carbon-based nanocomposite materials have been found to be very suitable for the detection of
Cd(II) ions due to their boosted electron transportation and high surface, leading towards high sensitivity
and high selectivity.
Understanding Isoniazid Crystals Agglomeration Through Quality by Design and Artificial Neural Network Analysis
Authors: Garala Kevinkumar , Raval Mihir , Patel Priya , Prajapati Bhupendra , Dharamsi Abhay
Published: October 2024

Introduction:

The aims of this study were to determine and govern critical sources of
variability in the process and to investigate the effect of excipients and processing conditions on
the critical quality attributes (CQAs) of isoniazid (INZ) crystal agglomerates using a quality-bydesign
(QbD) paradigm along with risk-based approach.

Methods:

The QbD paradigm is thoroughly exercised to determine the CQAs and to, link these
CQAs to agglomerate properties and to recognize potentially significant input variables. Considering
this, a risk assessment tool was executed with different excipients and processing conditions
to define their effect on CQAs of agglomerates. Potential risk factors were recognized using an
Ishikawa diagram and then investigated using principal component analysis and an artificial neural
network. After that, all agglomerates were optimized using the design of the experiment.

Results:

The optimized INZ crystal agglomerates were characterized using various tools such as
X-ray diffractometry, Fourier transform infrared spectroscopy, scanning electron microscopy, differential
scanning calorimetry, gas chromatography, and stability testing. These characterizations
confirmed that INZ did not undergo any structural modifications in the agglomerates.

Conclusion:

The results indicate that the QbD principles and risk assessment tool provide a valuable
means to fully understand directly compressible INZ crystal agglomerates, which could be
considered an exceptional alternative to the granulation method.
Navigating Dry Eye Research: A Comprehensive Review of Etiology, Clinical Trials, Patents, and Recent Advancements
Authors: Pal Vindhya , Verma Sushma
Published: October 2024

Background : Millions of people worldwide suffer from dry eye disease. Dry eye, a
multifunctional condition of the ocular surface, typically occurs in conjunction with an unbalanced
tear film. With increasing age, the dry eye problem becomes worse. Aqueous-deficit dry
eye and evaporative dry eye are the two traditional classifications for dry eye. Various examination
tools are used to diagnose dry eye. Clinical trials are conducted in four phases to check the
safety and efficacy of drugs. The quick clearance from the precorneal space is ensured by the eye's
advanced defense mechanism. It restricts the integrated medicine's entry into the eyes, resulting in
a usually low bioavailability for topical eyedrops. In this study, we focus on recently developed
formulations for curing dry eye.

Objective : This review's goal was to outline the etiology, clinical discovery and development, patents,
and recent advancements for dry eye disease.

Results : The current study has described the widespread incidence of dry eye, which was found
to be more common as people aged and recently developed formulations are treating dry eyes. According
to research, novel formulations are enhancing ocular drug delivery.

Conclusion : In this review, etiology, clinical data, dry eye formulation patents, and recent advancements
are all included.