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Diagnostic Efficacy of Serum Squamous Cell Carcinoma Antigen for Cancerous and Noncancerous Diseases: A Single-Center Experience in China
No full textBackground: Although squamous cell carcinoma antigen (SCCA) is a tumor biomarker used in the diagnosis of cancer, it is also elevated in non-oncological diseases. However, the diagnostic efficiency of SCCA for different diseases has yet to be systematically investigated. The purpose of this study was to explore the diagnostic efficacy of serum SCCA in neoplastic and non-neoplastic diseases. Methods: The clinical, pathological, and serological data for 15,844 patients admitted to Hainan Hospital of PLA General Hospital between November 2018 and May 2022 were collected and retrospectively analyzed. Results: Patients diagnosed with cervical cancer, bladder cancer, esophageal cancer, lung cancer, psoriasis, uremia, chronic renal failure, and nephritis had a mean serum SCCA value which exceeded the upper limit of the reference range (2.0 ng/mL). Squamous cell carcinoma (SCC) had considerably higher serum SCCA levels than other pathological types. The severity of renal failure is positively associated with a gradual increase in serum SCCA levels. Multivariate logistic analysis showed that SCCA was an indicator of uremia [odds ratio (OR), 1.845; 95% confidence interval (CI): 1.040–2.100; p = 0.038]. Receiver operating characteristic (ROC) curves demonstrated that the sensitivity (Sen) of SCCA in the diagnosis of uremia and psoriasis was 89.80% and 86.73%, respectively, and the specificity (Spe) was 75.00% and 78.79%, respectively. The area under the ROC curve (AUC) (95% CI) was 0.920 (0.882–0.958) and 0.907 (0.841–0.974), respectively, which was higher than cervical SCC [Sen: 81.63%; Spe: 68.46%, AUC (95% CI): 0.751 (0.609–0.793)]. Calculations of positive and negative likelihood ratios also supported these findings. Conclusions: While SCCA is a specific marker for SCC, its diagnostic accuracy is higher for noncancerous diseases such as uremia, psoriasis, and renal failure, indicating the need for clinicians to consider the correlation between SCCA and certain noncancerous diseases while evaluating tumor development and monitoring therapeutic efficacy
DUSP5 Protects against Diabetes-Related Heart Failure via Inhibiting PPARα-Mediated Fatty Acid Oxidation
Get PDFBackground: Heart failure (HF) is one of the most common complications of diabetes mellitus. This study aimed to investigate the potential roles of dual specificity phosphatase 5 (DUSP5), a negative regulator of mitogen-activated protein kinase signaling, in diabetes-related HF. Methods: Sprague dawley rats were randomly divided into the sham group, streptozotocin (STZ) group, STZ + vector group, STZ + Ad-DUSP5 group and vehicle group, and a group that was intravenously administered DUSP5-nanoparticle (NP) that carried the peroxisome proliferator-activated receptor alpha (PPARα) antagonist GW-6471. Triphenyl tetrazolium chloride staining was used to analyze the infarct area. The apoptosis of cardiomyocytes was determined using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling assay. For in vitro assays, mRNA expression was determined using quantitative reverse transcription-PCR; protein expression was detected using western blotting; protein localization was determined using immunofluorescence assay; and cell apoptosis was analyzed using flow cytometry. Results: DUSP5 expression was decreased in patients with diabetes-related HF, as well as in the in vitro model (p < 0.05). However, overexpression of DUSP5 inhibited the apoptosis of cardiomyocytes and fatty acid oxidation (p < 0.05). Moreover, DUSP5 mediated the nuclear translocation of PPARα (p < 0.05). By contrast, overexpression of PPARα promoted fatty acid oxidation and the apoptosis of cardiomyocytes (p < 0.05). The in vivo assay showed that DUSP5 overexpression inhibited the infarct area and death of cardiomyocytes (p < 0.05). Additionally, DUSP5-NP that delivered GW-6471 markedly alleviated heart damage induced by diabetes mellitus (p < 0.05). Conclusions: Our findings suggest that DUSP5 exerts a protective effect on diabetes-related HF by suppressing PPARα-dependent fatty acid oxidation. Therefore, DUSP5 may be a potential target for diabetes-related HF
Cimifugin Mitigates Allergic Response and Inflammatory Response in Allergic Rhinitis via Modulation of SIRT2
No full textBackground: Allergic rhinitis (AR) is a common autoimmune disease of the upper airway accompanied by prominent comorbid conditions. Cimifugin is a major constituent of Saposhnikovia divaricatae that is widely implied in the treatment of allergic diseases. This study aims to investigate the impacts of cimifugin on the process of AR and to ascertain the indistinct underlying mechanisms. Methods: Initially, AR mice models were developed and allergic symptoms in mice were observed. Hematoxylin and eosin (H&E) staining and toluidine blue staining were employed to assess the infiltration of eosinophils and mast cells in the nasal mucosa tissues of mice. Moreover, serum ovalbumin (OVA)-specific immunoglobulins levels, and levels of Th2 and Th1 cytokines were evaluated in the nasal lavage fluid using their corresponding enzyme-linked immunosorbent assay (ELISA) Kits. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay and western blot analysis were used to examine cell apoptosis. Furthermore, western blot analysis was used to determine the expression level of Sirtuin 2 (SIRT2) both in vitro and in vivo. Additionally, cell counting kit-8 (CCK-8) assay was utilized to examine cell viability and ELISA was used to estimate inflammatory levels. Moreover, reverse transcription-quantitative PCR (RT-qPCR), western blot analysis and IF assay were employed to determine the expression levels of mucin 5AC (MUC5AC). Results: It was noticed that cimifugin eased allergic symptoms and nasal mucosal inflammation, declined serum OVA-specific immunoglobulins and Th2 cytokines levels, and suppressed apoptosis in the OVA-induced AR murine model. Moreover, the cimifugin targeted SIRT2 and fortified SIRT2 expression both in vitro and in vivo. Furthermore, SIRT2 interference reversed the impacts of cimifugin on the inflammation and mucus production in interleukin-13 (IL-13)-exposed human nasal epithelial cells (hNECs). Conclusion: In conclusion, the cimifugin protected against OVA-triggered allergic symptoms and inflammation in AR by elevating SIRT2 expression
MEX3A Drives Triple-Negative Breast Cancer Migration, Invasion, and Metastasis by Interacting with NTRK1
No full textBackground: Triple-negative breast cancer (TNBC) stands out as the most aggressive form of breast cancer due to its significant propensity for metastasis. Exploring the molecular mechanisms of TNBC metastasis is essential to develop TNBC therapeutic strategies. Mex-3 RNA Binding Family Member A (MEX3A) has been recognized to promote TNBC proliferation. However, its role in TNBC metastasis hasnt been investigated. Methods: We investigated MEX3A levels in breast cancer cells, normal mammary tissues, and breast cancer tissues using Western blot analysis. Moreover, immunohistochemistry (IHC) analysis was used to determine MEX3A levels in TNBC tissues. Cell migration and invasion assays and lung metastasis assay were performed to investigate the role of MEX3A in TNBC metastasis in vitro and in vivo. Additionally, Co-immunoprecipitation was used to determine the interacting proteins of MEX3A. Results: MEX3A was upregulated in TNBC tissues compared to the normal mammary tissues, especially in TNBC tissues. Patients with high MEX3A expression exhibited shorter overall survival, distant metastasis-free-, relapse-free-, and post-progression survival time than those with low MEX3A expression (p < 0.05). MEX3A knockdown inhibited TNBC cell migration and invasion in vitro (p < 0.05). MEX3A overexpression promoted TNBC metastasis in vivo (p < 0.05). Mechanistically, MEX3A could interact with Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), resulting in activation of Ras GTPase (Ras-GTP), AKT Serine/Threonine Kinase (AKT), and Extracellular signal-regulated kinase (ERK) pathways, thereby promoting TNBC metastasis. Additionally, Ras pathway inhibitor MCP110 reversed the effect of MEX3A overexpression on TNBC cell migration and invasion. Conclusion: MEX3A is upregulated in TNBC tissues and can serve as an independent prognostic factor for TNBC patients. MEX3A promotes TNBC cell migration, invasion, and metastasis by interacting with NTRK1, resulting in the activation of Ras, AKT, and ERK pathways. These findings offer a potential therapeutic target for patients with TNBC
Roles of CMA in Neurodegenerative Diseases: Regulation of Cell Organelles Homeostasis
No full textNeurodegenerative diseases (NDDs) pose a significant public health challenge due to the rapid aging of the global population. Common features of NDDs include the abnormal aggregation of different proteins and disruption of normal function of organelles. Chaperone-mediated autophagy (CMA), one of the main pathways of lysosomal-mediated proteolysis, selectively delivers cytosolic proteins with an exposed KFERQ-like motif into the lysosomal lumen for degradation. CMA is essential for maintaining neuronal homeostasis, and its dysfunction has been implicated in aging and NDDs. Recent studies have revealed several mechanisms by which CMA is involved in the pathogenesis of NDDs. This review summarized the current understanding of the fundamental processes and regulatory mechanisms of CMA. Furthermore, we elucidate the links between CMA and NDDs, primarily focusing on how CMA regulates the function of cellular organelles in the pathological process underlying NDDs. Targeting impaired CMA represents an attractive and promising therapeutic strategy for the treatment of NDDs
Platelet-Derived Growth Factor-BB Promotes Proliferation and Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells
Get PDFBackground: Previous research has indicated that platelet-rich plasma (PRP) promotes fracture healing and aids in the treatment of nonunion. A key component of PRP, platelet-derived growth factor BB (PDGF-BB), may play a crucial role in PRP, enhancing the biological functions of bone marrow mesenchymal stem cells (BMSCs). This study aims to investigate whether PDGF-BB is a key effector in PRP that promotes proliferation and osteogenic differentiation of BMSCs. Methods: Rat BMSCs were isolated and cultured, then expanded to the third generation for morphological observation. Flow cytometry analysis was conducted to assess the expression of CD44, CD29, CD45, and CD11b. The BMSCs were cultured under different conditions: the control group received only basic culture medium, while experimental groups received 10 ng/mL, 25 ng/mL, 50 ng/mL, 100 ng/mL, and 200 ng/mL PDGF-BB. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay at 1, 3, 5, 7, and 10 days. The optimal PDGF-BB concentration was determined based on the CCK-8 results for subsequent experiments. Blood was collected from the rats heart and used to prepare and activate platelet-rich plasma (PRP), which was then stored in liquid nitrogen for later use. According to the culture conditions for BMSCs, the experimental groups were as follows: a blank control group, a 10% PRP group, a 50 ng/mL PDGF-BB group, and a 10% PRP + 100 μM AG1295 [platelet-derived growth factor β receptor (PDGFR-β) inhibitor] group. Each experimental group was replicated three times. Cell proliferation was assessed using the CCK-8 assay, the cell cycle was analyzed using flow cytometry, and the expression of osteogenic differentiation markers was evaluated by Western blot. Results: The cell viability of BMSCs treated with 50 ng/mL of PDGF-BB for 5 days was significantly higher than that of other concentration groups and time points. CCK-8 and flow cytometry results indicated that compared to the control group, both 10% PRP and 50 ng/mL PDGF-BB significantly promoted BMSCs proliferation and increased the proportion of BMSCs in the S phase of the cell cycle. Western blot results demonstrated that compared to the control group, both 10% PRP and 50 ng/mL PDGF-BB significantly upregulated the protein expression levels of osteogenic differentiation markers. The use of the PDGFR-β inhibitor AG1295 markedly attenuated the proliferative and osteogenic effects of 10% PRP on BMSCs. Conclusions: A concentration of 50 ng/mL PDGF-BB significantly enhances the proliferation and osteogenic differentiation of rat BMSCs. PDGF-BB may play a key role in PRP, contributing to the enhancement of BMSCs proliferation and osteogenic differentiation
A review of the progress for hydrocarbon migration technology: Mainstream methods, frontier trends, and future prospects
Get PDFOil and natural gas, as fluid minerals, flow within the Earth’s crust under the influence of various driving forces such as pressure, buoyancy, and gravity. This phenomenon is known as hydrocarbon migration. Hydrocarbon migration is a crucial component of the reservoir formation process, and accurately analyzing its direction affects the precision of trap prediction, well positioning, reservoir size, and morphology evaluation, thereby influencing the difficulty and cost of hydrocarbon development. However, most of the currently discovered hydrocarbon reservoirs have undergone multiple transformations or destructions, increasing the challenges of hydrocarbon development. Through an extensive literature review, this paper summarizes and categorizes the main current methods of studying hydrocarbon migration, including sedimentological methods, geochemical tracers, numerical simulation, and geophysical methods. Furthermore, this paper discusses and explores the frontier trends in hydrocarbon migration, mainly reflected in artificial intelligence (AI) methods, digital oil fields, geological big data analysis, and high-resolution seismic imaging technology. Looking to the future, there are significant opportunities in hydrocarbon migration research in data integration and intelligent analysis, high-resolution detection technology, digitization and automation, and the application of green technologies. However, there are also severe challenges regarding data quality and integration, the complexity and uncertainty of models, environmental and safety concerns, technology costs, and interdisciplinary collaboration. In conclusion, this paper clarifies the hydrocarbon migration process by reviewing, summarizing, and analyzing existing literature to understand hydrocarbon reservoirs’ formation and distribution patterns. It also delves into the mainstream methods, frontier trends, and prospects of hydrocarbon migration technology, providing valuable insights for future research
Editorial: Navigating the convergence of AI and the Metaverse
Get PDFAs we present Volume 5, Issue 2 of Metaverse, we find ourselves at a pivotal juncture where artificial intelligence (AI) and the metaverse intersect, heralding transformative changes across various domains. This edition delves into the multifaceted applications of AI within the metaverse, exploring its potential to revolutionize manufacturing, education, cultural heritage conservation, and beyond. The convergence of AI and the metaverse is not merely a technological phenomenon but a philosophical and cultural shift that reflects humanity’s aspirations for a more interconnected and intelligent future. As Alan Turing, often regarded as the father of AI, stated, “Instead of trying to produce a program to simulate the adult mind, why not rather try to produce one which simulates the child’s?” [1]. This underscores the boundless possibilities of creativity and learning inherent in AI—qualities that now extend into the immersive landscapes of the metaverse
Analytical economic study of rice supply response in Egypt
Get PDFRecent studies have identified several challenges associated with rice production, which hinder the achievement of self-sufficiency in rice. As a crop that heavily relies on irrigation water, rice production has implications for the nation’s water security. Nevertheless, there is still hope for reducing the future food gap by implementing agricultural policies that encourage farmers to increase production. Therefore, it has become essential to understand the responsiveness of rice cultivation area supply to changes, as this is crucial for making decisions regarding agricultural policies related to production and farm prices during the period from 2010 to 2023. The aim is to estimate farmers’ responsiveness, and the time required to achieve this response, as well as the supply elasticity. To achieve the research objective, both descriptive and quantitative statistical analysis were used, applying the Stepwise method in its logarithmic form to estimate the Supply Response. The elasticity of supply response for the rice cultivation area was estimated to be approximately 1.86% in the short term and 2.09% in the long term. It was also found that the response time of the cultivated rice area supply in Egypt to changes is low, estimated at around 1.12. This may be due to the inability to expand the cultivated area of this crop in the following year, as rice cultivation requires large amounts of water, posing a challenge given the scarcity of water resources. Additionally, farmers aim to maximize profits from the crops they cultivate
Enabling gender responsive low-carbon transport in India using SDG5 framework
Get PDFGender and mobility are strongly related and address challenges of safety and accessibility for women. Studies worldwide highlight the need to create more gender-responsive transport systems that maximize women’s mobility, civic participation, and safety. Gender inequality in urban transport is evident in Indian cities in terms of women’s longer walking trip lengths, longer time spent in commute and hence time poverty, impoverished health, and compromised personal safety. Even the public transport systems, often perceived as more gender-equal, overlook women’s needs and mobility concerns such as affordability and scheduling. This article presents transportation challenges faced by women (recorded through primary surveys and focus-group discussions) and further investigates how low-carbon urban transport, as perceived under the Paris Agreement and Sustainable Development Goals (SDGs), can be delivered with gender-equitable outcomes. For a more holistic perspective, the assessment is grounded in two Indian cities, Surat (4.5 million population), a fast-growing industrial metropolis, and Udaipur (0.5 million population), a small but important tourist destination in the nation