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Curcumin Improves Chemotherapy Resistance in Breast Cancer Cells via Inhibiting the Secretion of FGF2/FGFR2 from Cancer-Associated Fibroblasts
No full textBackground: Curcumin is an active ingredient isolated from the turmeric with anti-tumor activity. Cancer-associated fibroblasts (CAFs) can promote the development of chemical resistance in tumor cells. The present study aimed to explore the effect and molecular mechanism of curcumin on the chemosensitivity of breast cancer (BC). Methods: BC cell lines (MCF-7 and MDA-231) and paclitaxel (PTX)-resistant cell lines (MCF-7/PTX and MDA-231/PTX) were initially subjected to treatment with either curcumin or PTX. The cell proliferation and apoptosis rates were subsequently evaluated using Cell Counting Kit-8 (CCK-8) and flow cytometry. Western blotting was employed to evaluate the protein expression of fibroblast growth factor 2 (FGF2) and specific receptor-FGF receptor 2 (FGFR2). Because of the involvement of certain factors secreted by CAFs in chemotherapy resistance, the BC cells were exposed to a conditioned medium derived from CAFs (CAFs-CM). Subsequently, the changes in PTX resistance were monitored following interventions with both CAFs-CM and curcumin. Results: Curcumin blocked the proliferation (p < 0.01) and promoted apoptosis in BC cells (p < 0.01). Moreover, it reduced the proliferation (p < 0.01) and augmented the apoptosis (p < 0.01) in MCF-7/PTX and MDA-231/PTX cells after PTX intervention by inhibiting the expression of FGF2 and FGFR2. CAFs-CM enhanced PTX resistance in BC cells, while the phenomenon was reversed by curcumin. Moreover, CAFs-CM induced an increase in FGF2 and FGFR2 protein expression in BC cells (p < 0.01), and this effect was eliminated after curcumin treatment (p < 0.01). Conclusions: Curcumin increases BC cell sensitivity to PTX by inhibiting the secretion of FGF2/FGFR2 from CAFs
Saturated Hydrogen-Rich Saline Inhibits Ferroptosis to Ameliorate Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion via System Xc-/GSH/GPX4 Pathway
No full textBackground: Chronic cerebral hypoperfusion (CCH) induces mild cognitive impairment and contributes to the progression of vascular dementia and Alzheimers disease. Hydrogen has demonstrated protective effects against various neurological disorders. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, plays a significant role in this context. This study aimed to investigate the impact of saturated hydrogen-rich saline (HRS) on cognitive deficits and explore potential mechanisms following CCH. Methods: CCH was induced in rats via two-vessel occlusion, and the animals were subsequently treated with saturated HRS. Cognitive function was assessed using the Morris water maze. The neuronal morphology and number in the hippocampus were evaluated through hematoxylin and eosin (H&E) staining, Nissl staining, and immunofluorescence of neuronal nuclear protein (NeuN) and microtubule-associated protein 2 (MAP2). Neuronal ultrastructure was observed under a transmission electron microscope. Lipid peroxide biomarkers were measured to estimate lipid peroxide injury. Iron accumulation was detected using Perls Prussian Blue (PPB) staining. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to determine iron metabolism and ferroptosis-associated factors. Mechanism validation involved the administration of Ferrostatin-1, Erastin, and RAS-selective lethal 3 (RSL3), inhibitors of ferroptosis, cystine/glutamate antiporter (System Xc-) and glutathione peroxidase 4 (GPX4), respectively. Results: HRS reduced cell death in the hippocampal region of CCH rats, restored the ruptured outer mitochondrial membrane of neurons, and increased levels of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), GPX4, and solute carrier family 7 member 11 (SLC7A11), while decreasing Malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE). Additionally, iron deposition was reduced in HRS-treated CCH rats. HRS inhibited ferroptosis, as evidenced by upregulation of ferritin light chain (FTL) and ferritin heavy chain (FTH1), and down-regulation of transcription factor (TF), transferrin receptor 1 (TFR1), solute carrier family 11 member 2 (DMT1), Iron responsive element binding protein 2 (IREB2), and prostaglandin-endoperoxide synthase 2 (PTGS2). The inhibition of ferroptosis induced by HRS was mimicked by Ferrostatin-1. Erastin or RSL3 simulated CCH-induced neuronal injury and ferroptosis, which were alleviated by HRS. Conclusion: HRS improved cognitive impairment by suppressing ferroptosis in hippocampal neurons through the System Xc-/GSH/GPX4 pathway following CCH, suggesting its potential as a novel therapeutic agent for CCH treatment
Helicobacter pylori Accelerates the Occurrence and Development of Gastric Adenocarcinomas by Regulating the MiR-146a-5p/FHL1 Axis
No full textBackground: Gastric cancer (GC) is a common malignancy of the digestive tract and about 95% of them are gastric adenocarcinomas (STAD). However, Helicobacter pylori (HP) infection does not only serve as a major risk factor for GC but is also linked to the differential expression of miRNAs. Moreover, miR-146a-5p has a crucial role in numerous human malignancies. Therefore, this study aimed to explore the molecular mechanisms underlying the role of miR-146a-5p in HP-associated STAD. Methods: MiRNAs genes linked to HP-induced GC were retrieved from the GeneCards and g: Profiler databases. MiR-146a-5p expression in HP-induced STAD was determined using quantitative real-time PCR. The role of miR-146a-5p in HP-induced STAD was assessed using Cell Counting Kit-8, colony formation assay, wound healing analysis, transwell analysis, flow cytometry, and Western blot. Furthermore, the mechanism of miR-146a-5p in STAD was evaluated using a dual-luciferase reporter assay. Results: MiR-146a-5p expression was significantly increased in HP-infected STAD cells. Moreover, HP infection promoted STAD cell growth by increasing the expression of miR-146a-5p. Mechanistically, miR-146a-5p targeted four-and-a-half LIM domain protein 1 (FHL1), and rescue assays further authenticated that HP facilitated STAD cell growth by increasing miR-146a-5p to reduce FHL1. Conclusion: In summary, HP infection leads to elevated miR-146a-5p expression and promotes STAD by mediating the miR-146a-5p/FHL1 pathway. This study might provide a basis for considering miR-146a-5p as a diagnostic marker for STAD and may help in designing preventive measures and treatment strategies
Impact of Exosomes on the Pathogenesis of Diabetes and Its Complications
No full textDiabetes mellitus (DM) encompasses a range of metabolic disorders characterized by chronic hyperglycemia, including type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). The pathophysiology of DM is intricate, exhibiting variations across its different types, involving factors such as autoimmunity, insulin resistance, and β-cell dysfunction. Prolonged hyperglycemia in DM leads to microvascular and macrovascular complications, driven by various pathophysiological processes such as inflammation, coagulation, oxidative stress, and endothelial dysfunction. Exosomes, a specific type of extracellular vesicles (EVs), are recognized contributors to the aforementioned pathological processes and are thus implicated in the pathogenesis of diabetes and its associated complications. This work begins with summarizing the key characteristics, biogenesis, composition, and essential physiological and pathological functions of exosomes. It then focuses on collating and analyzing the most recent data on the pathogenic roles of exosomes in T1DM, T2DM, GDM, and diabetes-associated complications, such as diabetic retinopathy, nephropathy, neuropathy, and cardiomyopathy
The role of generative AI in cyber security
Full text linkIn the ever-evolving landscape of cyber threats, the integration of Artificial Intelligence (AI) has become popular into safeguarding digital assets and sensitive information for organisations throughout the world. This evolution of technology has given rise to a proliferation of cyber threats, necessitating robust cybersecurity measures. Traditional approaches to cybersecurity often struggle to keep pace with these rapidly evolving threats. To address this challenge, Generative Artificial Intelligence (Generative AI) has emerged as a transformative sentinel. Generative AI leverages advanced machine learning techniques to autonomously generate data, text, and solutions, and it holds the potential to revolutionize cybersecurity by enhancing threat detection, incident response, and security decision-making processes. We explore here the pivotal role that Generative AI plays in the realm of cybersecurity, delving into its core concepts, applications, and its potential to shape the future of digital security
Enhanced inclusion and accessibility in education and training through virtual worlds
Full text linkBased on the evolution of immersive technologies, both in software and hardware, this article proposes a methodology for creating accessible and inclusive virtual worlds, with potential impacts on education, training, and lifelong learning. Through this paradigm, the combination of real and virtual cosmos generates new challenges in accessibility and inclusion. The co-existence of virtuality in tangible real life could be extended respectively in a wide spectrum of everyday life for enhanced inclusion and accessibility. New business models and even more accessible services in training and education could be raised through this suggestion. Metaverse, omniverse, and the advancements in extended reality equipment are the main allies in this endeavor. Artificial intelligence and enhanced experiences via advanced immersion could find easily their role in the context of meaningful virtual worlds in lifelong learning. As we are in the dove of the Metaverse era this is a unique opportunity to build accessible and inclusive virtual worlds from the very beginning
Exploring post-COVID-19 travel intentions of foreign tourists in Nepal: An empirical study using structural equation modeling
Full text linkAmidst the global challenges posed by the rapid transmission of a new coronavirus, the tourism sector has undergone an unprecedented downturn, similar to all economic sectors. In light of this, the present study aims to examine the travel intentions of foreign tourists in the post-COVID-19 era in the Kathmandu Valley of Nepal using Social Cognitive Theory. Structural equation modeling was used for data analysis of 350 tourists. The study revealed that the travel intention after the COVID-19 outbreak was significantly influenced by severity perception and personal positive effects, both of which were shaped by environmental changes. Results indicate that a common challenge faced by tourists was the lack of quality hotels and homestays, and the suggested managerial solution was to increase the number and enhance the quality of available accommodations. Tourism in Nepal serves as an enduring source of national income, offering a significant competitive advantage, thus rendering sustainable tourism unavoidable
Predicting sustainability for slowtourism events
Full text linkThe increasing demand for slow tourism in rural regions is leading many organizations to reorganize events by planning new strategies able to predict the impact of incoming visitors and new stakeholders. Typical economic benefit-cost analysis often cannot be used in such contexts in which it is hard to predict socio-economic impacts that are the most relevant. In this way, a methodology like the SROI Method, based on a wide set of indicators and a flexible analytical method, could give a prediction estimation useful to predict socio-economic impacts and tailored for a wide set of people. In this paper we consider three examples taken from small villages around Rome for which a set of events has been analyzed through a revised SROI Method in which we calculate the corresponding SROI value and compare it under a set of revised stages named as—SMARTOUR SROI focused on Slow Tourism Planning. The proposed evaluation methodology obtained by the application of the SROI Method to smart tourism stages is a first example of new sustainable analysis for slow tourism. The result shows that the methodology always gives a positive evaluation by highlighting the main issues related to the impact of slow tourism in such emerging scenarios. Moreover, in the discussion we can show that the case of the historical train example gives the best result due to the particular impact of such a typical scenario
Current status, performance characteristics and future perspective of electric tractor
Full text linkElectric tractors with its cutting-edge technological improvements represent a transformative shift in agricultural technology for achieving the broad objectives of sustainable and environment friendly farming practices. This review examines the current status, performance characteristics, and future perspectives of electric tractors, focusing on their potential to replace traditional diesel models. The analysis highlights the advantages of electric tractors, including lower operational costs, reduced maintenance, and zero emissions, which contribute to quieter and cleaner agricultural operations. This transformation is witnessing several challenges in terms of high initial costs, limited battery life and the need for extensive charging infrastructure. The performance of electric tractors, particularly in extreme climates, is also a significant concern, with battery efficiency and power output varying under different environmental conditions. Despite these challenges, advancements in battery technology and propulsion systems, along with supportive government policies, are paving the way for greater adoption of electric tractors. The review also discusses the variability in regional adoption rates, with Europe leading due to strong regulatory support, while other regions like North America and Asia-Pacific are witnessing sluggish growth. The integration of electric tractors into precision agriculture and smart farming systems presents exciting opportunities for the future, boosting both productivity and sustainability. The investment in innovations and infrastructure related to electric tractor and renewed supportive policies from the governmental sector can usher a revolution in agricultural production system with lower environmental impact
Unraveling the ecological footprint of textile dyes: A growing environmental concern
Full text linkThe textile industry, being a giant consumer of water and chemicals, uses synthetic dyes on a wide scale because of their low cost and wide color gamut. In contrast, synthetic dyes have shown great environmental hazards. A notable feature of textile dyes is their resistance to biodegradation, which contributes to long-lasting pollution in water, soil, and the atmosphere. The water body ecosystems are contaminated with dye-laden wastewater resulting from textile manufacturing. Photosynthetic activity is prevented, hence decreasing oxygen levels in water and drastically affecting aquatic life. Moreover, improper sludge disposal containing dyes leads to the degradation of soil quality, impacting plant health and microbial activities. Such pollutants can exhibit bioaccumulation in organisms, enhancing toxicity via the food chain and presenting serious health risks to humans, including carcinogenic effects and genetic malfunction. The paper reviews new developments related to ecologically friendly dyes, advanced wastewater treatments, and circular economies involving dye recycling and waterless dyeing techniques that are key to reducing the environmental impact of these dyes. Also needed is rigid enforcement of regulations coupled with the wider diffusion of sustainable technologies to minimize environmental damage in the textile industry and protect natural ecosystems and human health