Search Results (1,375)

Endometriosis is a disease characterized by the presence of endometrial glands and stroma outside of the uterine corpus, often clinically presenting with pain and/or infertility. Ectopic lesions exhibit features characteristic of epithelial-to-mesenchymal transition (EMT), a process in which epithelial cells lose polarity and acquire mesenchymal traits, including migratory and invasive capabilities. During the process of EMT, epithelial traits are downregulated, while mesenchymal traits are acquired, with cells developing migratory ability, increasing proliferation, and resistance to apoptosis. EMT is promoted by exposure to hypoxia and stimulation by transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), and estradiol. Signaling pathways that promote EMT are activated in most ectopic lesions and involve transcription factors such as Snail, Slug, ZEB-1/2, and TWIST-1/2. EMT-specific molecules present in the serum of women with endometriosis appear to have diagnostic potential. Strategies targeting EMT in animal models of endometriosis have demonstrated regression of ectopic lesions, opening the door for novel therapeutic approaches. This review summarizes the current understanding of the role of EMT in endometriosis and highlights potential targets for EMT-related diagnosis and therapeutic interventions. Full article

In the context of the valorization of agri-food by-products, tomato (Solanum lycopersicum L.) seeds represent a protein-rich matrix containing potential bioactives. The aim of the present work is to develop a biochemical pipeline for (i) achieving high protein recovery from tomato seed, (ii) optimizing the hydrolysis with different proteases, and (iii) characterizing the resulting peptides. This approach was instrumental for obtaining and selecting the most promising peptide mixture to test for antifungal activity. To this purpose, proteins from an alkaline extraction were treated with bromelain, papain, and pancreatin, and the resulting hydrolysates were assessed for their protein/peptide profiles via SDS-PAGE, SEC-HPLC, and RP-HPLC. Bromelain hydrolysate was selected for antifungal tests due to its greater quantity of peptides, in a broader spectrum of molecular weights and polarity/hydrophobicity profiles, and higher DPPH radical scavenging activity, although all hydrolysates exhibited antioxidant properties. In vitro assays demonstrated that the bromelain-digested proteins inhibited the growth of Fusarium graminearum and F. oxysporum f.sp. lycopersici in a dose-dependent manner, with a greater effect at a concentration of 0.1 mg/mL. The findings highlight that the enzymatic hydrolysis of tomato seed protein represents a promising strategy for converting food by-products into bioactive agents with agronomic applications, supporting sustainable biotechnology and circular economy strategies. Full article

The search for sustainable, economically viable, and effective plant protection strategies against pathogenic bacteria, fungi, and viruses is a major challenge in modern agricultural practices. Chitosan (CS) is an abundant cationic natural biopolymer known for its biocompatibility, low toxicity, and antimicrobial properties. Its potential use in agriculture for pathogen control is a promising alternative to traditional chemical fertilisers and pesticides, which raise concerns regarding public health, environmental protection, and pesticide resistance. This study focused on the preparation of chitosan nanoparticles (CS-NPs) through cross-linking with organic molecules, such as tannic acid (TA). Various formulations were explored for the development of stable nanoscale particles having encapsulation capabilities towards low compounds of varying polarity and with potential agricultural applications relevant to plant health and growth. The solution properties of the NPs were assessed using dynamic and electrophoretic light scattering (DLS and ELS); their morphology was observed through atomic force microscopy (AFM), while analytical ultracentrifugation (AUC) measurements provided insights into their molar mass. Their properties proved to be primarily influenced by the concentration of CS, which significantly affected its intrinsic conformation. Additional structural insights were obtained via infrared and UV–Vis spectroscopic measurements, while detailed fluorescence analysis with the use of three different probes, as model cargo molecules, provided information regarding the hydrophobic and hydrophilic microdomains within the particles. Full article

This research focuses on designing polymer membranes as biocompatible materials using home-built electrospinning equipment, offering alternative solutions for tissue regeneration applications. This technological development supports cell growth on biomaterial substrates, including hepatocellular carcinoma (Hep-G2) cells. This work researches the compatibility of polymer membranes (fiber mats) made of polyvinylidene difluoride (PVDF) for possible use in cellular engineering. A standard culture medium was employed to support the proliferation of Hep-G2 cells under controlled conditions (37 °C, 4.8% CO₂, and 100% relative humidity). Subsequently, after the incubation period, electrochemical impedance spectroscopy (EIS) assays were conducted in a physiological environment to characterize the electrical cellular response, providing insights into the biocompatibility of the material. Scanning electron microscopy (SEM) was employed to evaluate cell adhesion, morphology, and growth on the PVDF polymer membranes. The results suggest that PVDF polymer membranes can be successfully produced through electrospinning technology, resulting in the formation of a dipole structure, including the possible presence of a polar β-phase, contributing to piezoelectric activity. EIS measurements, based on R_ct and C_dl values, are indicators of ion charge transfer and strong electrical interactions at the membrane interface. These findings suggest a favorable environment for cell proliferation, thereby enhancing cellular interactions at the fiber interface within the electrolyte. SEM observations displayed a consistent distribution of fibers with a distinctive spherical agglomeration on the entire PVDF surface. Finally, integrating piezoelectric properties into cell culture systems provides new opportunities for investigating the influence of electrical interactions on cellular behavior through electrochemical techniques. Based on the experimental results, this electrospun polymer demonstrates great potential as a promising candidate for next-generation biomaterials, with a probable application in tissue regeneration. Full article

Titanium alloys are frequently subjected to surface treatments to enhance their biocompatibility and corrosion resistance in biological environments. Plasma electrolytic oxidation (PEO) is an environmentally friendly electrochemical technique capable of forming oxide layers characterized by high corrosion resistance, biocompatibility, and strong adhesion to the substrate. In this study, the PEO process was performed using a low-melting-point ternary eutectic electrolyte composed of Ca(NO₃)₂–NaNO₃–KNO₃ (41–17–42 wt.%) with the addition of ammonium dihydrogen phosphate (ADP). The use of this electrolyte system enables a reduction in the operating temperature from 280 to 160 °C. The effects of applied voltage from 200 to 400V, current frequency from 50 to 1000 Hz, and ADP concentrations of 0.1, 0.5, 1, 2, and 5 wt.% on the growth of titanium oxide composite coatings on a Ti-6Al-4V substrate were investigated. The incorporation of Ca and P was confirmed by phase and chemical composition analysis, while scanning electron microscopy (SEM) revealed a porous surface morphology typical of PEO coatings. Corrosion resistance in Hank’s solution, evaluated via Tafel plot fitting of potentiodynamic polarization curves, demonstrated a substantial improvement in electrochemical performance of the PEO-treated samples. The corrosion current decreased from 552 to 219 nA/cm², and the corrosion potential shifted from −102 to 793 mV vs. the Reference Hydrogen Electrode (RHE) compared to the uncoated alloy. These findings indicate optimal PEO processing parameters for producing composite oxide coatings on Ti-6Al-4V alloy surfaces with enhanced corrosion resistance and potential bioactivity, which are attributed to the incorporation of Ca and P into the coating structure. Full article

The interleukin-20 (IL-20) cytokine subfamily, a subset of the IL-10 superfamily, includes IL-19, IL-20, IL-22, IL-24, and IL-26. Recently, their involvement in cancer biology has gained attention, particularly due to their impact on the tumor microenvironment (TME). Notably, IL-20 subfamily cytokines can exert both pro-tumorigenic and anti-tumorigenic effects, depending on the context. For example, IL-22 promotes tumor growth by enhancing cancer cell proliferation and protecting against apoptosis, whereas IL-24 demonstrates anti-tumor activity by inducing cancer cell death and inhibiting metastasis. Additionally, these cytokines influence macrophage polarization—an essential factor in the immune landscape of tumors—thereby modulating the inflammatory environment and immune evasion strategies. Understanding the dual role of IL-20 subfamily cytokines within the TME and their interactions with cancer cell hallmarks presents a promising avenue for therapeutic development. Interleukin-20 receptor antagonists are being researched for their role in cancer therapy, since they potentially inhibit tumor growth and progression. This review explores the relationship between IL-20 cytokines and key cancer-related processes, including growth and proliferative advantages, angiogenesis, invasion, metastasis, and TME support. Further research is necessary to unravel the specific mechanisms underlying their contributions to tumor progression and to determine their potential for targeted therapeutic strategies. Full article

This work presents an innovative hydrothermal approach for fabricating flexible piezoelectric PZT thin films on 20 μm titanium foil substrates using TiO₂ and SrTiO₃ (STO) interlayers. Three heterostructures (Ti/PZT, Ti/TiO₂/PZT, and Ti/TiO₂/STO/PZT) were synthesized to enable low-temperature growth and improve ferroelectric performance for advanced flexible MEMS. Characterizations including XRD, PFM, and P–E loop analysis evaluated crystallinity, piezoelectric coefficient d₃₃, and polarization behavior. The results demonstrate that the multilayered Ti/TiO₂/STO/PZT structure significantly enhances performance. XRD confirmed the STO buffer layer effectively reduces lattice mismatch with PZT to ~0.76%, promoting stable morphotropic phase boundary (MPB) composition formation. This optimized film exhibited superior piezoelectric and ferroelectric properties, with a high d₃₃ of 113.42 pm/V, representing an ~8.65% increase over unbuffered Ti/PZT samples, and displayed more uniform domain behavior in PFM imaging. Impedance spectroscopy showed the lowest minimum impedance of 8.96 Ω at 10.19 MHz, indicating strong electromechanical coupling. Furthermore, I–V measurements demonstrated significantly suppressed leakage currents in the STO-buffered samples, with current levels ranging from 10⁻¹² A to 10⁻⁹ A over ±3 V. This structure also showed excellent fatigue endurance through one million electrical cycles, confirming its mechanical and electrical stability. These findings highlight the potential of this hydrothermally engineered flexible heterostructure for high-performance actuators and sensors in advanced MEMS applications. Full article

Impedance-based cellular assays allow determination of biological functions of cell populations in real-time by measuring electrical impedance. As compared to end-point assays, such as trans-epithelial electrical resistance assays, for example, they enable fast, non-invasive, and easy detection of cell kinetics—their growth, attachment, and interaction can be monitored over time. In our experiment, Caco-2 cells were cultured on E-plates 16. Next, fully differentiated cells were treated with either TNF-α or 3,4-dihydroxy-L-phenylalanine (L-DOPA). We aimed to verify the possibility of real-time testing of the viability, monolayer formation, and integrity (i.e., the presence of a functional and polarized monolayer) of Caco-2 cells by the xCELLigence real-time cell analyzer (RTCA) S16 system (Agilent Technologies). Full article

Tumor-associated macrophages (TAMs) play a critical role in the tumor microenvironment (TME), interacting with cancer cells and other components to promote tumor growth. Given the influence of TAMs on tumor progression and resistance to therapy, regulating the activity of these macrophages is crucial for improving cancer treatment outcomes. TAMs often exhibit immunosuppressive phenotypes (commonly referred to as M2-like macrophages), which suppress immune responses and contribute to drug resistance. Therefore, inhibiting immunosuppressive polarization offers a promising strategy to impede tumor growth. This study revealed retinoic acid receptor gamma (RARγ), a nuclear receptor, as a key regulator of immunosuppressive polarization in THP-1 macrophages. Indeed, the inhibition of RARγ, either by a small molecule or gene silencing, significantly reduced the expression of immunosuppressive macrophage markers. In a three-dimensional tumor spheroid model, immunosuppressive macrophages enhanced the proliferation of HCT116 colorectal cancer cells, which was significantly hindered by RARγ inhibition. These findings suggest that targeting RARγ reprograms immunosuppressive macrophages and mitigates the tumor-promoting effects of TAMs, highlighting RARγ as a promising therapeutic target for developing novel anti-cancer strategies. Full article

The renin–angiotensin–aldosterone system (RAAS) plays a central role in cardiovascular and renal homeostasis and is increasingly recognized for its broad immunomodulatory effects. Pharmacological RAAS inhibition, primarily via angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), has demonstrated therapeutic value beyond its use in hypertension and heart failure, extending to autoimmune, infectious, oncologic, and neurodegenerative conditions. ACEIs and ARBs modulate both innate and adaptive immune responses through Ang II-dependent and -independent mechanisms, influencing macrophage polarization, T-cell differentiation, cytokine expression, and antigen presentation. Notably, ACEIs exhibit Ang II-independent effects by enhancing antigen processing and regulating amyloid-β metabolism, offering potential neuroprotective benefits in Alzheimer’s disease. ARBs, particularly telmisartan and candesartan, provide additional anti-inflammatory effects via PPARγ activation. In cancer, RAAS inhibition affects tumor growth, angiogenesis, and immune surveillance, with ACEIs and ARBs showing distinct yet complementary impacts on tumor microenvironment modulation and chemotherapy cardioprotection. Moreover, ACEIs have shown promise in autoimmune myocarditis, colitis, and diabetic nephropathy by attenuating inflammatory cytokines. While clinical evidence supports the use of centrally acting ACEIs to treat early cognitive decline, further investigation is warranted to determine the long-term outcomes across disease contexts. These findings highlight the evolving role of RAAS inhibitors as immunomodulatory agents with promising implications across multiple systemic pathologies. Full article

Diabetic foot ulcers (DFUs), which affect approximately 15% of individuals with diabetes mellitus (DM), result from complex molecular disturbances involving chronic hyperglycemia, immune dysfunction, and infection. At the molecular level, chronic hyperglycemia promotes the formation of advanced glycation end products (AGEs), activates the AGE-RAGE-NF-κB axis, increases oxidative stress, and impairs macrophage polarization from the pro-inflammatory M1 to the reparative M2 phenotype, collectively disrupting normal wound healing processes. The local wound environment is further worsened by antibiotic-resistant polymicrobial infections, which sustain inflammatory signaling and promote extracellular matrix degradation. The rising threat of antimicrobial resistance complicates infection management even further. Recent studies emphasize that optimal glycemic control using antihyperglycemic agents such as metformin, Glucagon-like Peptide 1 receptor agonists (GLP-1 receptor agonists), and Dipeptidyl Peptidase 4 enzyme inhibitors (DPP-4 inhibitors) improves overall metabolic balance. These agents also influence angiogenesis, inflammation, and tissue regeneration through pathways including AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and vascular endothelial growth factor (VEGF) signaling. Evidence indicates that maintaining glycemic stability through continuous glucose monitoring (CGM) and adherence to antihyperglycemic treatment enhances antibiotic effectiveness by improving immune cell function and reducing bacterial virulence. This review consolidates current molecular evidence on the combined effects of glycemic and antibiotic therapies in DFUs. It advocates for an integrated approach that addresses both metabolic and microbial factors to restore wound homeostasis and minimize the risk of severe outcomes such as amputation. Full article

To obtain a flat top shaped passband in a conventional thin-film-based optical bandpass filter (OBF), it needs a large number of constitutional layers of thin films, which makes the film deposition systems more complicated and accumulates errors in film growth. A flat top and polarization-independent optical bandpass filter structure is proposed based on experimentally verified polarization independency in the form of a prism-pair coupled planar optical waveguide (POW). The POW is composed of two waveguide stacks, which consists of nine planar thin-film layers. Theoretical simulations show that the flat band top spans about 5 nm with transmittance over 97.8%. The passband is designed to be centered at 632.8 nm, the He-Ne laser wavelength, and the FWHM (full width at half maximum) bandwidth is about 35 nm. Within 0.5° tuning for the incident angle of the light, the passband could be shifted within 50 nm, while its transmittance fluctuates only less than 1% and the passband shape distorts only slightly. This type of OBF is potentially applicable in various fields of optical and laser spectroscopies. Full article

Background: TNBC patients respond poorly to chemotherapy, leading to high mortality rates and a worsening prognosis. Here, we investigated the effect of M-I on TNBC tumor growth suppression and its potential mechanisms. Methods: Signaling pathways were analyzed to study the effect of M-I on TNBC cells (human MDA-MB-231 and mouse 4T1). We used orthotopic mouse models to examine the anti-tumor efficacy of M-I. Tumor volume and the status of tumor-associated macrophages (TAMs) were assessed by qRT-PCR or FACS analysis. Results: We found a significant dose- and time-dependent inhibition of TNBC cell proliferation following treatment with M-I. Cell cycle analysis revealed a shortened S phase in M-I-treated cells and downregulation of AURKA, PLK1, CDC25c, CDK1, and cyclinB1. Furthermore, M-I treatment reduced the expression of pSTAT3, cyclinD1, and c-Myc in TNBC cells. To evaluate the anti-tumor efficacy of M-I, we employed orthotopic TNBC mouse models and observed a significant reduction in tumor growth without measurable toxicity. Next, we analyzed RNA from control and M-I-treated tumors to further assess the status of TAMs and observed a significant decrease in M2-like macrophages in the M-I-treated group. Immortalized bone marrow-derived mouse macrophages (iMacs) exposed to conditioned media (CM) of TNBC cells with or without M-I treatment indicated that the M-I treated CM of TNBC cells significantly reduce the M2phenotype in iMacs. Mechanistically, we found that M-I specifically targets the IL-4/MAPK signaling axis to reduce immunosuppressive M2 macrophage polarization. Conclusions: Our study reveals a novel mechanism by which M-I inhibits TNBC cell proliferation by regulating intracellular signaling and altering TAMs in the tumor microenvironment and highlights its potential as a promising candidate for TNBC therapy. Full article

Grounded in coupling theory, this study investigates the interplay among three key elements of economic growth, namely the digital economy, carbon emissions efficiency, and high-quality economic development. Drawing on data from 30 Chinese provinces from 2000 to 2023, we employ exploratory spatiotemporal data analysis and the GeoDetector model to examine the spatial–temporal evolution and underlying driving forces of coupling coordination. This research enriches the theoretical framework of multi-system synergistic development in a green transition context and offers empirical insights and policy recommendations for fostering regional coordination and sustainable development. The results reveal that (1) both the digital economy and high-quality economic development show a steady upward trend, while carbon emissions efficiency has a “U-shaped” curve pattern; (2) at the national level, the degree of coupling coordination has evolved over time from “mild disorder” to “on the verge of disorder” to “barely coordinated,” while at the regional level, this pattern of coupling coordination shifts over time from “Eastern–Northeastern–Central–Western” to “Eastern–Central–Northeastern–Western”; (3) although spatial polarization in coupling coordination has improved, disparities fluctuate in a “decline–rise” pattern, with interregional differences being the main source of that variation; (4) the degree of coupling coordination has a positive spatial correlation, but with a declining trend with fluctuations; and (5) improvements in the level of economic development, human capital, industrial structure, green technological innovation, and market development capacity all contribute positively to coupling coordination. Among them, green technological innovation and market development capacity are the most influential drivers, and the interactions among all driving factors further enhance their collective impact. Full article

High-quality growth of the construction industry and an improved human settlements environment are essential to sustainable urbanization. Existing studies have paid limited systematic attention to the spatial and temporal dynamics of the coordinated development between the construction industry and human settlements, as well as the underlying factors driving regional disparities. This gap restricts the formulation of precise, differentiated sustainable policies tailored to regions at different development stages and with varying resource endowments. Southern China, characterized by pronounced spatial heterogeneity and unique development trends, offers a natural laboratory for examining the spatio-temporal interaction between these two dimensions. Using panel data for 15 southern provinces (2013–2022), we applied the entropy method, coupling coordination model, Dagum Gini coefficient, spatial trend surface analysis, gravity model, and grey forecasting to evaluate current conditions and predict future trends. The main findings are as follows. (1) The coupling coordination degree rose steadily, forming a stepped spatial pattern from the southwest through the center to the southeast. (2) The coupling coordination degree appears obvious polarization effect, presenting a spatial linkage pattern with Jiangsu-Shanghai-Zhejiang, Hubei-Hunan-Jiangxi, and Sichuan-Chongqing as the core of the three major clusters. (3) The overall Dagum Gini coefficient declined, but intra-regional disparities persisted: values were highest in the southeast, moderate in the center, and lowest in the southwest; inter-regional differences dominated the total inequality. (4) Forecasts for 2023–2027 suggest further improvement in the coupling coordination degree, yet spatial divergence will widen, creating a configuration of “eastern leadership, central catch-up acceleration, and differentiated southwestern development.” This study provides an evidence base for policies that foster high-quality construction sector growth and enhance the living environment. The findings of this study indicate that policymaking should prioritize promoting synergistic regional development, enhancing the radiating and driving role of core regions, and establishing a multi-level coordinated governance mechanism to bridge regional disparities and foster more balanced and sustainable development. Full article