Search Results (8)

Understanding the molecular targets of natural products is crucial for elucidating their mechanisms of action, mitigating toxicity, and uncovering potential therapeutic pathways. Icaritin (ICT), a bioactive flavonoid, demonstrates significant anti-tumor activity but lacks defined molecular targets. This study employs an advanced strategy integrating proteolysis targeting chimera (PROTAC) technology with quantitative proteomics to identify ICT’s key targets. A library of 22 ICT-based PROTAC derivatives were synthesized, among which LJ-41 exhibited a superior IC50 of 5.52 μM against Burkitt lymphoma (CA-46) cells. Then, differential proteomic analysis identified Bax inhibitor-1 (BI-1) as a potential target. Target validation techniques, including cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, surface plasmon resonance (SPR) assay, and molecular docking, confirmed LJ-41’s high specificity for BI-1. Mechanistic investigations revealed that LJ-41 induces apoptosis through BI-1 degradation, triggering endoplasmic reticulum stress and activating inositol-requiring enzyme 1 α (IRE1α), activating transcription factor 6 (ATF6), and nuclear factor erythroid 2-related factor transcription factor heme oxygenase 1 (NRF2-HO-1) signaling pathways. This study establishes a refined methodological framework for natural product target discovery and highlights ICT-PROTAC derivatives’ potential for clinical application in Burkitt lymphoma treatment. Full article

This study evaluated the factors influencing IgG/IgM antibody levels in 120 patients with head and neck cancer (HNC) following vaccination with inactivated SARS-CoV-2 vaccines. Each patient’s demographic and clinical data were documented, and serum IgG and IgM antibodies were detected using a commercial magnetic chemiluminescence enzyme immunoassay kit. The results indicated that while all patients had received at least one vaccine dose, 95 tested positive for IgG and 25 were negative. A higher proportion of IgG-positive patients had received three vaccine doses. Comparatively, gamma-glutamyl transferase levels were elevated in IgM-negative patients. The study further differentiated patients based on their treatment status: 46 were treatment-naive and 74 had received chemotherapy combined with immune checkpoint inhibitors (ICT) at enrollment. Despite similar baseline characteristics and time from vaccination to antibody detection, IgM positivity was significantly lower in the ICT group, with no significant difference in IgG positivity between the treatment-naive and ICT groups. A multivariable analysis identified the number of vaccine doses as an independent factor of IgG positivity, while ICT emerged as an independent risk factor for IgM positivity. Additionally, IgG titers generally declined over time, although patients with higher baseline IgG levels maintained higher titers longer. In conclusion, ICT in patients with HNC does not significantly affect IgG levels post-vaccination. However, booster vaccinations have been shown to be associated with higher IgG positivity, although these levels gradually decrease over time. Full article

UICC stage IV small-cell lung cancer (SCLC) is a highly aggressive malignancy without curative treatment options. Several randomized trials have demonstrated improved survival rates through the addition of checkpoint inhibitors to first-line platin-based chemotherapy. Consequently, a combination of chemo- and immunotherapy has become standard palliative treatment. However, no reliable predictive biomarkers for treatment response exist. Neither PD-L1 expression nor tumor mutational burden have proven to be effective predictive biomarkers. In this study, we compared the cellular immune statuses of SCLC patients to a healthy control cohort and investigated changes in peripheral blood B, T, and NK lymphocytes, as well as several of their respective subsets, during treatment with immunochemotherapy (ICT) using flow cytometry. Our findings revealed a significant decrease in B cells, while T cells showed a trend to increase throughout ICT. Notably, high levels of exhausted CD4+ and CD8+ cells, alongside NK subsets, increased significantly during treatment. Furthermore, we correlated decreases/increases in subsets after two cycles of ICT with survival. Specifically, a decrease in Th17 cells indicated a better overall survival. Based on these findings, we suggest conducting further investigation into Th17 cells as a potential early predictive biomarkers for response in patients receiving palliative ICT for stage IV SCLC. Full article

Breast cancer is one of the most prevalent malignancies and the leading cause of cancer-associated mortality in China. Icaritin (ICT), a prenyl flavonoid derived from the Epimedium Genus, has been proven to inhibit the proliferation and stemness of breast cancer cells. Our previous study demonstrated that IC2, a derivative of ICT, could induce breast cancer cell apoptosis by Stearoyl-CoA desaturase 1 (SCD1) inhibition. The present study further investigated the mechanism of the inhibitory effects of IC2 on breast cancer cells in vitro and in vivo. Our results proved that IC2 could stimulate autophagy in breast cancer cells with the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling and mitogen-activated protein kinase (MAPK) signaling. Combination treatment of the AMPK inhibitor decreased IC2-induced autophagy while it markedly enhanced IC2-induced apoptosis. In common with IC2-induced apoptosis, SCD1 overexpression or the addition of exogenous oleic acid (OA) could also alleviate IC2-induced autophagy. In vivo assays additionally demonstrated that IC2 treatment markedly inhibited tumor growth in a mouse breast cancer xenograft model. Overall, our study was the first to demonstrate that IC2 induced cytoprotective autophagy by SCD1 inhibition in breast cancer cells and that the autophagy inhibitor markedly enhanced the anticancer activity of IC2. Therefore, IC2 was a potential candidate compound in combination therapy for breast cancer. Full article

The banking sector has been considered as one of the primary adopters of Information and Communications Technologies. Especially during the last years, they have invested a lot into the digital transformation of their business process. Concerning their retail customers, banks realized very early the great potential abilities to provide value added self-services functions via mobile devices, mainly smartphones to them; thus, they have invested a lot into m-banking apps’ functionality. Furthermore, the COVID-19 pandemic has brought out different ways for financial transactions and even more mobile users have taken advantage of m-banking app services. Thus, the purpose of this empirical paper is to investigate the determinants that impact individuals on adopting or not m-banking apps. Specifically, it examines two groups of individuals, users (adopters) and non-users (non-adopters) of m-banking apps, and aims to reveal if there are differences and similarities between the factors that impact them on adopting or not this type of m-banking services. To our knowledge, this is the second scientific attempt where these two groups of individuals have been compared on this topic. The paper proposes a comprehensive conceptual model by extending Venkatech’s et al. (2003) Unified Theory of Acceptance and Use of Technology (UTAUT) with ICT facilitators (i.e., reward and security) and ICT inhibitors (i.e., risk and anxiety), as well as the recommendation factor. However, this study intends to fill the research gap by investigating and proving for the first time the impact of social influence, reward and anxiety factors on behavioral intention, the relationship between risk and anxiety and the impact of behavioral intention on recommendation via the application of Confirmatory Factor Analysis and Structural Equation Modeling (SEM) statistical techniques. The results reveal a number of differences regarding the factors that impact or not these two groups towards m-banking app adoption; thus, it provides new insights regarding m-banking app adoption in a slightly examined scientific field. Thus, the study intends to assist the banking sector in better understanding their customers with the aim to formulate and apply customized m-business strategies and increase not only the adoption of m-banking apps but also the level of their further use. Full article

In the last few years, a number of social media e-business models including the social networking giants of Facebook, Pinterest and Instagram have offered direct purchase abilities to both their users and the involved enterprises. Hence, individuals can buy directly without having to leave the social media website. At the same time, there is a significant increase in the number of online purchases through mobile devices. To add to this, nowadays, the vast majority of internet users prefer to surf via their smartphone rather than a desktop PC. The aforementioned facts reveal the abilities and potential dynamics of Mobile Social Commerce (MSC), which is considered not only the present but also the future of e-commerce, as well as an area of prosperous academic and managerial concern. In spite of its several extant abilities and its booming future, MSC has been little examined until now. Therefore, this study aims to determine the factors that impact smartphone users’ behavioral intention to adopt direct purchases through social media apps in a country where these kinds of m-services are not yet available. In specific, it extends the well-established Unified Theory of Acceptance and Use of Technology (UTAUT) model with the main ICT facilitators (i.e., convenience, reward and security) and inhibitors (i.e., risk and anxiety). The suggested conceptual model aims to increase the understanding on the topic and strengthen the importance of this major type of MSC. Convenience sampling was applied to gather the data and Structural Equation Modeling (SEM) was then performed to investigate the research hypotheses of the proposed conceptual model. The results show that performance expectancy exerts a positive impact on behavioral intention. Furthermore, all ICT facilitators examined do impact significantly on smartphone users’ decision to adopt direct mobile purchases through social media apps, whereas anxiety exerts a negative effect. Full article

Between 2018 and 2023 the penetration rate of electricity smart meters in the European Union (EU) is expected to grow from approximately 44% to 71%. The unprecedently rapid development of smart metering (SM) as an ICT-enabled technological novelty is progressing in a complex, multi-actor innovation system, which is strongly driven by EU-level institutions and policies. This paper presents the comprehensive Technology Innovation System (TIS) analysis of electricity SM development in the EU, with a focus placed on regulatory aspects. The article identifies the key elements of the SM innovation system (technologies and infrastructures; actors and networks; institutions and policies) and characterises their interaction based on an in-depth desk research and a critical assessment of regulations, statistics and primary and grey literature sources (e.g., market reports). The main enablers and barriers for EU-level SM TIS development are studied. The major driving force for EU-level SM TIS is the clear, yet evolving vision of EU-level actors for the SM deployment, founded on the grounds of energy conservation and empowerment of customers. On the other hand, the major inhibitor is the insufficient regulatory framework for roll-outs at the level of a Member State, which does not fully ensure interoperability, data protection and security standards or organisational effectiveness. Full article

Immune checkpoint inhibitor therapy (ICT) is a new treatment strategy developed for the treatment of cancer. ICT inhibits pathways known to downregulate the innate immune response to cancer cells. These drugs have been shown to be effective in the treatment of a variety of cancers, including metastatic melanoma and lung cancer. Challenges in response evaluation of patients in ICT have risen as immune related side effects and immune cell infiltration may be confused with progressive disease. Furthermore, the timing of the evaluation scan may be challenged by relatively slow responses. To overcome this, new response criteria for evaluating these patients with morphologic imaging have been proposed. The aim of this paper is to review and discuss the current evidence for the use of molecular imaging, e.g., PET/CT (Positron Emission Tomography/Computer Tomography) with ¹⁸F-Fluorodeoxyglucoes (FDG) as an alternative imaging method for monitoring patients undergoing ICT. Following the currently available evidence, this review will primarily focus on patients with malignant melanoma. Full article