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A high mortality rate was found in cancer patients with distant metastasis. Development of targeted drugs for effectively inhibiting cancer metastasis is the key for increasing therapeutic success. In the current study, a folding paper system was developed to mimic a tumor–vascular interface for the study of long-distance cell migration. Correlation between the cell migration distance and metastasis-associated gene was successfully analyzed by disassembling the stacked paper construct. The result revealed that the migration distance and number of migrated cells were highly correlated to cell characteristics. Moreover, immunocytochemistry was directly conducted on the paper layer to study the signaling pathway. Kelch-like and protein tyrosine phosphatase families were examined and the PTPN13 gene was shown to regulate long-distance cell migration. By analyzing the phosphorylated mTOR, the PTPN13 gene was further confirmed to be a tumor suppressor gene that inhibits long-distance cell migration. The folding paper system provides an alternative approach for long-distance cell migration. Metastasis-associated gene expression can be analyzed to potentially develop targeted drugs for cancer metastasis inhibition. [ABSTRACT FROM AUTHOR]

In recent years, cell migration assays (CMAs) have emerged as a tool to study the migration of cells along with their physiological responses under various stimuli, including both mechanical and bio-chemical properties. CMAs are a generic system in that they support various biological applications, such as wound healing assays. In this paper, we review the development of the CMA in the context of its application to wound healing assays. As such, the wound healing assay will be used to derive the requirements on CMAs. This paper will provide a comprehensive and critical review of the development of CMAs along with their application to wound healing assays. One salient feature of our methodology in this paper is the application of the so-called design thinking; namely we define the requirements of CMAs first and then take them as a benchmark for various developments of CMAs in the literature. The state-of-the-art CMAs are compared with this benchmark to derive the knowledge and technological gap with CMAs in the literature. We will also discuss future research directions for the CMA together with its application to wound healing assays. [ABSTRACT FROM AUTHOR]

Cold atmospheric plasma (CAP) technology has emerged as a revolutionary therapeutic technology in dermatology, recognized for its safety, effectiveness, and minimal side effects. CAP demonstrates substantial antimicrobial properties against bacteria, viruses, and fungi, promotes tissue proliferation and wound healing, and inhibits the growth and migration of tumor cells. This paper explores the versatile applications of CAP in dermatology, skin health, and skincare. It provides an in-depth analysis of plasma technology, medical plasma applications, and CAP. The review covers the classification of CAP, its direct and indirect applications, and the penetration and mechanisms of action of its active components in the skin. Briefly introduce CAP's suppressive effects on microbial infections, detailing its impact on infectious skin diseases and its specific effects on bacteria, fungi, viruses, and parasites. It also highlights CAP's role in promoting tissue proliferation and wound healing and its effectiveness in treating inflammatory skin diseases such as psoriasis, atopic dermatitis, and vitiligo. Additionally, the review examines CAP's potential in suppressing tumor cell proliferation and migration and its applications in cosmetic and skincare treatments. The therapeutic potential of CAP in treating immune-mediated skin diseases is also discussed. CAP presents significant promise as a dermatological treatment, offering a safe and effective approach for various skin conditions. Its ability to operate at room temperature and its broad spectrum of applications make it a valuable tool in dermatology. Finally, introduce further research is required to fully elucidate its mechanisms, optimize its use, and expand its clinical applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is one of the most common causes of death worldwide. Today, this disease does not have an effective treatment, leading to the exploration of novel pharmacological molecules. In this paper, we design and synthesize with a new synthetic route the lipophilic cation derived from gallic acid (TPP+C10) and gentisic acid (GA-TPP+C10), both able to reach mitochondria and uncouple the electron transport chain. Our results show that combining 5-fluorouracil with GA-TPP+C10 has a synergistic cytotoxic effect on CRC cells. Both compounds show antimigratory effects, decreasing signaling pathways and biomarkers. Our results show that mitochondrial agents could be an alternative to standard CRC drugs against this disease. Colorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC—such as 5-fluorouracil (5FU)—remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP+C10), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP+C10), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP+C10 with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP+C10 and TPP+C10 using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP+C10 and TPP+C10, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP+C10 and GA-TPP+C10 increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity. [ABSTRACT FROM AUTHOR]

Intermediate filaments are one of three polymeric structures that form the cytoskeleton of epithelial cells. In the epithelium, these filaments are made up of a variety of keratin proteins. Intermediate filaments complete a wide range of functions in keratinocytes, including maintaining cell structure, cell growth, cell proliferation, cell migration, and more. Given that these functions are intimately associated with the carcinogenic process, and that hyperkeratinization is a quintessential feature of oral leukoplakias, the utility of keratins in oral leukoplakia is yet to be fully explored. This scoping review aims to outline the current knowledge founded on original studies on human tissues regarding the expression and utility of keratins as diagnostic, prognostic, and predictive biomarkers in oral leukoplakias. After using a search strategy developed for several scientific databases, namely, PubMed, Scopus, Web of Science, and OVID, 42 papers met the inclusion and exclusion criteria. One more article was added when it was identified through manually searching the list of references. The included papers were published between 1989 and 2024. Keratins 1–20 were investigated in the 43 included studies, and their expression was assessed in oral leukoplakia and dysplasia cases. Only five studies investigated the prognostic role of keratins in relation to malignant transformation. No studies evaluated keratins as a diagnostic adjunct or predictive tool. Evidence supports the idea that dysplasia disrupts the terminal differentiation pathway of primary keratins. Gain of keratin 17 expression and loss of keratin 13 were significantly observed in differentiated epithelial dysplasia. Also, the keratin 19 extension into suprabasal cells has been associated with the evolving features of dysplasia. The loss of keratin1/keratin 10 has been significantly associated with high-grade dysplasia. The prognostic value of cytokeratins has shown conflicting results, and further studies are required to ascertain their role in predicting the malignant transformation of oral leukoplakia. [ABSTRACT FROM AUTHOR]

This article is an interview with Tiffany Roach and Kari Lenhart, researchers at Drexel University, about their study on the effects of stress on germ stem cells in Drosophila. They found that repeated mating stress induces reversible changes in the germ stem cell niche. The researchers also discuss their future plans to study the effects of stress on other stem cell niches and collaborate with scientists working in different organisms. Overall, their work provides insights into the impact of stress on stem cell populations. [Extracted from the article]

Macrophage alternative activation is involved in kidney fibrosis. Previous researches have documented that the transcriptional regulators Yes‐associated protein (Yap)/transcriptional coactivator with PDZ‐binding motif (Taz) are linked to organ fibrosis. However, limited knowledge exists regarding the function and mechanisms of their downstream molecules in regulating macrophage activation and kidney fibrosis. In this paper, we observed that the Hippo pathway was suppressed in macrophages derived from fibrotic kidneys in mice. Knockout of Taz or Tead1 in macrophages inhibited the alternative activation of macrophages and reduced kidney fibrosis. Additionally, by using bone marrow–derived macrophages (BMDMs), we investigated that knockout of Taz or Tead1 in macrophages impeded both cell proliferation and migration. Moreover, deletion of Tead1 reduces p‐Smad3 and Smad3 abundance in macrophages. And chromatin immunoprecipitation (ChIP) assays showed that Tead1 could directly bind to the promoter region of Smad3. Collectively, these results indicate that Tead1 knockout in macrophages could reduce TGFβ1‐induced phosphorylation Smad3 via transcriptional downregulation of Smad3, thus suppressing macrophage alternative activation and IRI‐induced kidney fibrosis. [ABSTRACT FROM AUTHOR]

Fucoxanthin is a carotenoid, reddish-brown in color, which is mainly derived from marine organisms such as brown algae and diatoms, and has aroused extensive scientific interest due to its unique chemical structure and abundant biological activities. Studies have shown that fucoxanthin processes significant anti-inflammatory and anti-cancer activities. Its anti-inflammatory mechanisms primarily include inhibiting oxidative stress, regulating inflammatory factors, inducting cell autophagy, and resisting cell apoptosis, etc. The main mechanism of anti-cancer activity includes inducing cell autophagy and apoptosis mechanisms, regulating the cell cycle, inhibiting cell migration, and suppressing cell invasion, among other aspects. In this paper, the research progress of anti-inflammatory and anti-cancer activities and related mechanisms of action of fucoxanthin is briefly summarized, which provides the theoretical basis and reference for further research and development of fucoxanthin. [ABSTRACT FROM AUTHOR]

Cell migration is known to be a fundamental biological process, playing an essential role in development, homeostasis, and diseases. This paper introduces a cell tracking algorithm named HFM-Tracker (Hybrid Feature Matching Tracker) that automatically identifies cell migration behaviours in consecutive images. It combines Contour Attention (CA) and Adaptive Confusion Matrix (ACM) modules to accurately capture cell contours in each image and track the dynamic behaviors of migrating cells in the field of view. Cells are firstly located and identified via the CA module-based cell detection network, and then associated and tracked via a cell tracking algorithm employing a hybrid feature-matching strategy. This proposed HFM-Tracker exhibits superiorities in cell detection and tracking, achieving 75% in MOTA (Multiple Object Tracking Accuracy) and 65% in IDF1 (ID F1 score). It provides quantitative analysis of the cell morphology and migration features, which could further help in understanding the complicated and diverse cell migration processes. [ABSTRACT FROM AUTHOR]

A novel Gd-MOF based on tetrafluoro-terephthalic acid has been synthesized and its structure has been solved using X-ray single crystal diffraction data. The compound, with the formula [Gd2(F4BDC)3·H2O]·DMF, is isostructural with other Ln-MOFs based on the same ligand and has been recently reported. Its crystals were also reduced to nanometer size by employing acetic acid or cetyltrimethylammonium bromide (CTAB) as a modulator. The relaxometric properties of the nanoparticles were evaluated in solution by measuring 1H T1 and T2 as a function of the applied magnetic field and temperature. The biocompatibility of Gd-MOFs was evaluated on murine microglial BV-2 and human glioblastoma U251 cell lines. In both cell lines, Gd-MOFs do not modify the cell cycle profile or the activation levels of ERK1/2 and Akt, which are protein-serine/threonine kinases that participate in many signal transduction pathways. These pathways are fundamental in the regulation of a large variety of processes such as cell migration, cell cycle progression, differentiation, cell survival, metabolism, transcription, tumour progression and others. These data indicate that Gd-MOF nanoparticles exhibit high biocompatibility, making them potentially valuable for diagnostic and biomedical applications. [ABSTRACT FROM AUTHOR]

As an active metabolite of irinotecan, 7-ethyl-10-hydroxy-camptothecin (SN38) exhibits significantly stronger anticancer activity compared to irinotecan. However, its poor water solubility restricts its clinical use. Moreover, SN38 has only a weak effect on the metastasis of cancer cells. In the present work, a conjugate of SN38 with aminoguanidine was synthesized via a Cu-catalytic azide–alkyne click (CuAAC) reaction. As the sixth compound synthesized via the synthetic route, we here denoted the SN38-aminoguanidine conjugate as compound 6. Compound 6 is self-assembled into nanoparticles due to its amphiphilic structure. The resulting nanoparticles with a dynamic diameter of 134.05 ± 3.31 nm and a ξ of 1.27 ± 0.10 mV were irregular lumps of around 120 nm, as demonstrated by transmission electron microscopy (TEM), and significantly decreased the level of endogenous nitric oxide via inhibition of inducible nitric oxide synthase (iNOS). Compared with irinotecan, compound 6 showed much stronger cytotoxicity toward triple-negative breast cancer MDA-MB-231 cells while lower cytotoxicity against human normal breast epithelial MCF10A cells. More importantly, compound 6 significantly inhibited the migration of MDA-MB-231 cells while irinotecan did little at a dose of 0.5 μM. Once MDA-MB-231 cells were pretreated with a nitric oxide donor, the inhibitory effects of compound 6 on proliferation and migration of MDA-MB-231 cells both decreased, indicating that iNOS played an important role in proliferation and migration of breast cancer cells. In a molecular docking model, compound 6 formed two hydrogen bonds and one π–H interaction with topo1 in a different binding mode from camptothecin and SN38, while no interaction with the DNA of the topo1–DNA complex was observed. The lower docking score of compound 6 (−9.45), in contrast to that of SN38 (−8.82) suggested that topo1 was still an important target through which compound 6 exerted its antitumor activity. These findings indicated that the incorporation of aminoguanidine into SN38 was an effective strategy to simultaneously address the issue of poor water solubility and endow SN38 with antimigratory activity. [ABSTRACT FROM AUTHOR]

The editorial "Editors' showcase 2023: insights in cell adhesion and migration" published in Frontiers in Cell & Developmental Biology discusses the importance of cell adhesion for migration, focusing on both extracellular matrix and cell-to-cell adhesion. The research topic includes reviews and original research papers on various aspects of cell movement, such as cytoskeleton remodeling, molecular motor activity, and membrane trafficking. The editorial highlights the role of mechanotransduction, extracellular matrix, and molecular motor proteins in cell migration, providing insights into the complex mechanisms involved in this essential biological process. [Extracted from the article]

Mechanical stimuli play important roles on the growth, development, and behavior of tissue. A simple and novel paper-based in vitro tissue chip was developed that can deliver two types of mechanical stimuli—local compression and shear flow—in a programmed manner. Rat vascular endothelial cells (RVECs) were patterned on collagen-coated nitrocellulose paper to create a tissue chip. Localized compression and shear flow were introduced by simply tapping and bending the paper chip in a programmed manner, utilizing an inexpensive servo motor controlled by an Arduino microcontroller and powered by batteries. All electrical compartments and a paper-based tissue chip were enclosed in a single 3D-printed enclosure, allowing the whole device to be independently placed within an incubator. This simple device effectively simulated in vivo conditions and induced successful RVEC migration in as early as 5 h. The developed device provides an inexpensive and flexible alternative for delivering mechanical stimuli to other in vitro tissue models. [ABSTRACT FROM AUTHOR]

Cell-cell adhesion is one the most fundamental mechanisms regulating collective cell migration during tissue development, homeostasis, and repair, allowing cell populations to selforganize and eventually form and maintain complex tissue shapes. Cells interact with each other via the formation of protrusions or filopodia and they adhere to other cells through binding of cell surface proteins. The resulting adhesive forces are then related to cell size and shape and, often, continuum models represent them by nonlocal attractive interactions. In this paper, we present a new continuum model of cell-cell adhesion which can be derived from a general nonlocal model in the limit of short-range interactions. This new model is local, resembling a system of thin-film type equations, with the various model parameters playing the role of surface tensions between different cell populations. Numerical simulations in one and two dimensions reveal that the local model maintains the diversity of cell sorting patterns observed both in experiments and in previously used nonlocal models. In addition, it also has the advantage of having explicit stationary solutions, which provides a direct link between the model parameters and the differential adhesion hypothesis. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are specialized antigen-presenting cells that are crucial for maintaining self-tolerance, initiating immune responses against pathogens, and patrolling body compartments. Despite promising aspects, DC-based immunotherapy faces challenges that include limited availability, immune escape in tumors, immunosuppression in the tumor microenvironment, and the need for effective combination therapies. A further limitation in DC-based immunotherapy is the low population of migratory DC (around 5%–10%) that migrate to lymph nodes (LNs) through afferent lymphatics depending on the LN draining site. By increasing the population of migratory DCs, DC-based immunotherapy could enhance immunotherapeutic effects on target diseases. This paper reviews the importance of DC migration and current research progress in the context of DC-based immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that CCR7, an important inflammatory factor, can promote the proliferation and metastasis of oral squamous cell carcinoma (OSCC), but its role in the tumor microenvironment (TME) remains unclear. This paper explores the role of CCR7 in the TME of OSCC. Methods: In this work, we constructed CCR7 gene knockout mice and OSCC mouse models. Single-cell RNA sequencing (scRNA-seq) and bioinformatics were used to analyze the differences in the OSCC microenvironment between three CCR7 gene knockout mice (KO) and three wild-type mice (WT). Immunohistochemistry, immunofluorescence staining, and flow cytometry were used to analyze the expression of key genes in significantly different cell types between the KO and WT groups. An in vitro experiment was used to verify the effect of CCR7 on M2 macrophage polarization. Results: In the mouse OSCC models, the tumor growth rate in the KO group was significantly lower than that in the WT group. Eight main cell types (including tumor cells, fibroblasts, macrophages, granulocytes, T cells, endothelial cells, monocytes, and B cells) were identified by Seurat analysis. The scRNA-seq results showed that the proportion of tumor cells was lower, but the proportion of inflammatory cells was significantly higher in the KO group than in the WT group. CellPhoneDB analysis results indicated a strong interaction relationship between tumor cells and macrophages, T cells, fibroblasts, and endothelial cells. Functional enrichment results indicated that the expression level of the Dusp1 gene in the KO group was generally higher than that in the WT group in various cell types. Macrophage subclustering results indicated that the proportion of M2 macrophages in the KO group was lower than that in the WT group. In vitro experimental results showed that CCR7 can promote M2 macrophage polarization, thus promoting the proliferation, invasion and migration of OSCC cells. Conclusions: CCR7 gene knockout can significantly inhibit the growth of mouse oral squamous cell carcinoma by promoting the polarization of M2 macrophages. [ABSTRACT FROM AUTHOR]

In tissue formation and regeneration processes, cells often move collectively, maintaining connections through intercellular adhesions. However, the specific roles of cell–substrate and cell-to-cell mechanical interactions in the regulation of collective cell migration are not yet fully understood. Finite element modeling (FEM) may be a way to assess more deeply the biological, mechanical, and chemical phenomena behind cell adhesion. FEM is a powerful tool widely used to simulate phenomena described by systems of partial differential equations. For example, FEM provides information on the stress/strain state of a cell adhering to a substrate, as well as on its mechanobiological behavior. This review paper, after briefly describing basic principles of cell adhesion, surveys the most important studies that have utilized FEM to investigate the structural response of a cell adhering to a substrate and how the forces acting on the cell–substrate adhesive structures affect the global cell mechanical behavior. [ABSTRACT FROM AUTHOR]

Migrating cells in tissues are often known to exhibit collective swirling movements. In this paper, we develop an active vertex model with polarity dynamics based on contact inhibition of locomotion (CIL). We show that under this dynamics, the cells form steady-state vortices in velocity, polarity, and cell stress with length scales that depend on polarity alignment rate (ζ), self-motility (v0), and cell-cell bond tension (λ). When the ratio λ/v0 becomes larger, the tissue reaches a near jamming state because of the inability of the cells to exchange their neighbors, and the length scale associated with tissue kinematics increases. A deeper examination of this jammed state provides insights into the mechanism of sustained swirl formation under CIL rule that is governed by the feedback between cell polarities and deformations. To gain additional understanding of how active forcing governed by CIL dynamics leads to large-scale tissue dynamics, we systematically coarse-grain cell stress, polarity, and motility and show that the tissue remains polar even on larger length scales. Overall, we explore the origin of swirling patterns during collective cell migration and obtain a connection between cell-level dynamics and large-scale cellular flow patterns observed in epithelial monolayers. [ABSTRACT FROM AUTHOR]

Increased production of Prostaglandin D2 (PGD2) is linked to development and progression of asthma and allergy. PGD2 is rapidly degraded to its metabolites, which initiate type 2 innate lymphoid cells (ILC2) migration and IL-5/IL-13 cytokine secretion in a PGD2 receptor 2 (DP2)-dependent manner. Blockade of DP2 has shown therapeutic benefit in subsets of asthma patients. Cellular mechanisms of ILC2 activity in response to PGD2 and its metabolites are still unclear. We hypothesized that ILC2 respond non-uniformly to PGD2 metabolites. ILC2s were isolated from peripheral blood of patients with atopic asthma. ILC2s were stimulated with PGD2 and four PGD2 metabolites (Δ12-PGJ2, Δ12-PGD2, 15-deoxyΔ12,14-PGD2, 9α,11β-PGF2) with or without the selective DP2 antagonist fevipiprant. Total RNA was sequenced, and differentially expressed genes (DEG) were identified by DeSeq2. Differential gene expression analysis revealed an upregulation of pro-inflammatory DEGs in ILC2s stimulated with PGD2 (14 DEGs), Δ12-PGD2 (27 DEGs), 15-deoxyΔ12,14-PGD2 (56 DEGs) and Δ12-PGJ2 (136 DEGs), but not with 9α,11β-PGF2. Common upregulated DEGs were i.e. ARG2, SLC43A2, LAYN, IGFLR1, or EPHX2. Inhibition of DP2 via fevipiprant mainly resulted in downregulation of pro-inflammatory genes such as DUSP4, SPRED2, DUSP6, ETV1, ASB2, CD38, ADGRG1, DDIT4, TRPM2, or CD69. DEGs were related to migration and various immune response-relevant pathways such as "chemokine (C-C motif) ligand 4 production", "cell migration", "interleukin-13 production", "regulation of receptor signaling pathway via JAK-STAT", or "lymphocyte apoptotic process", underlining the pro-inflammatory effects of PGD2 metabolite-induced immune responses in ILC2s as well as the anti-inflammatory effects of DP2 inhibition via fevipiprant. Furthermore, PGD2 and metabolites showed distinct profiles in ILC2 activation. Overall, these results expand our understanding of DP2 initiated ILC2 activity. [ABSTRACT FROM AUTHOR]

This paper presents the findings of a comprehensive study exploring the synergistic effects arising from the combination of microwave ablation and pulsed electromagnetic field (PEMF) therapy on prostate cancer cells. The research encompassed five distinct experimental groups, with continuous electric field measurements conducted during the entire treatment process. Group 1 and Group 2, subjected to microwave power below 350 W, exhibited specific electric field values of 72,800 V/m and 56,600 V/m, respectively. In contrast, Group 3 and Group 4, exposed to 80 W microwave power, displayed electric field levels of approximately 1450 V/m, while remaining free from any observable electrical discharges. The migratory and invasive capacities of PC3 cells were assessed through a scratch test in all groups. Notably, cells in Group 3 and Group 4, subjected to the combined treatment of microwave ablation and PEMF, demonstrated significantly accelerated migration in comparison to those in Groups 1 and 2. Additionally, Group 5 cells, receiving PEMF treatment in isolation, exhibited decreased migratory ability. These results strongly suggest that the combined approach of microwave ablation and PEMF holds promise as a potential therapeutic intervention for prostate cancer, as it effectively reduced cell viability, induced apoptosis, and impeded migration ability in PC3 cells. Moreover, the isolated use of PEMF demonstrated potential in limiting migratory capacity, which could hold critical implications in the fight against cancer metastasis. In this study, a new approach to treat prostate cancer by combining microwave ablation (MWA) and pulsed electromagnetic field (PEMF) therapy is explored. We used specific devices like rectangular waveguides for MWA and circular coils for PEMF. The energy sources utilized in the study comprised a magnetron tube system, similar to the microwave source found in a microwave oven, for generating microwaves, and a signal generator for producing PEMF. We used specialized equipment for MWA and PEMF to maintain controlled conditions, ensuring precise and reliable results. The research included testing various groups of prostate cancer cells exposed to different intensities of microwave power and magnetic flux density. The movement of cancer cells in different groups was examined through a wound healing assay, where cancer cells were placed on a flat surface, and we observed whether they filled the gap created by their movement. Interestingly, cells treated with both MWA and PEMF demonstrated faster movement compared to cells treated with MWA alone or PEMF alone. This combined treatment not only effectively decreased cell movement but also showed the potential cell death. The results showed that the combination of MWA and PEMF suggest a promising therapeutic strategy. The findings contribute to the development of precise and effective therapies that could enhance patient outcomes and quality of life. However, further research and validation are essential before translating these findings into clinical applications. [ABSTRACT FROM AUTHOR]

Microfluidics approaches have gained popularity in the field of directed cell migration, enabling control of the extracellular environment and integration with live-cell microscopy; however, technical hurdles remain. Among the challenges are the stability and predictability of the environment, which are especially critical for the observation of fibroblasts and other slow-moving cells. Such experiments require several hours and are typically plagued by the introduction of bubbles and other disturbances that naturally arise in standard microfluidics protocols. Here, we report on the development of a passive pumping strategy, driven by the high capillary pressure and evaporative capacity of paper, and its application to study fibroblast chemotaxis. The paper pumps—flowvers (flow + clover)—are inexpensive, compact, and scalable, and they allow nearly bubble-free operation, with a predictable volumetric flow rate on the order of μl/min, for several hours. To demonstrate the utility of this approach, we combined the flowver pumping strategy with a Y-junction microfluidic device to generate a chemoattractant gradient landscape that is both stable (6+ h) and predictable (by finite-element modeling calculations). Integrated with fluorescence microscopy, we were able to recapitulate previous, live-cell imaging studies of fibroblast chemotaxis to platelet derived growth factor (PDGF), with an order-of-magnitude gain in throughput. The increased throughput of single-cell analysis allowed us to more precisely define PDGF gradient conditions conducive for chemotaxis; we were also able to interpret how the orientation of signaling through the phosphoinositide 3-kinase pathway affects the cells' sensing of and response to conducive gradients. [ABSTRACT FROM AUTHOR]

Simple Summary: TP is a widely utilized anticancer medication, particularly effective in treating HCC. Thorough investigation into TP's molecular mechanism in HCC treatment is crucial for precise and combination therapy. In this paper, we have unveiled a novel mechanism of TP in HCC treatment, where it inhibits tumor growth by reducing lipid accumulation. While the inhibition of P53 gene activity is commonly thought to be the reason for TP's effectiveness in treating HCC, this new mechanism serves as a significant complement to the current understanding, paving the way for innovative approaches to HCC treatment. Hepatocellular carcinoma (HCC), which is the third leading cause of cancer-related mortality in the world, presents a significant medical challenge. Triptolide (TP) has been identified as an effective therapeutic drug for HCC. However, its precise therapeutic mechanism is still unknown. Understanding the mechanism of action of TP against HCC is crucial for its implementation in the field of HCC treatment. We hypothesize that the anti-HCC actions of TP might be related to its modulation of HCC lipid metabolism given the crucial role that lipid metabolism plays in promoting the progression of HCC. In this work, we first demonstrate that, both in vitro and in vivo, TP significantly reduces lipid accumulation in HCC cells. Additionally, we notice that lipoprotein lipase (LPL) expression is markedly upregulated in HCC, and that its levels are positively connected with the disease's progression. It is interesting to note that TP dramatically reduces LPL activity, which in turn prevents HCC growth and reduces lipid accumulation. Additionally, the effect of TP on LPL is a direct correlation. These results definitely demonstrate that TP protects hepatocytes against abnormal accumulation of lipids by transcriptionally suppressing LPL, which reduces the development of HCC. This newly identified pathway provides insight into the process through which TP exerts its anti-HCC actions. [ABSTRACT FROM AUTHOR]

High-grade gliomas are considered an incurable disease. Despite all the various therapy options available, patient survival remains low, and the tumor usually returns. Tumor resistance to conventional therapy and stimulation of the migratory activity of surviving cells are the main factors that lead to recurrent tumors. When developing new treatment approaches, the effect is most often evaluated on standard and phenotypically depleted cancer cell lines. Moreover, there is much focus on the anti-proliferative effect of such therapies without considering the possible stimulation of migratory activity. In this paper, we studied how glioma cell migration changes after exposure to bi-(AID-1-T), an anti-proliferative aptamer. We investigated the effect of this aptamer on eight human glioma cell cultures (Grades III and IV) that were derived from patients' tumor tissue; the difference between primary and recurrent tumors was taken into account. Despite its strong anti-proliferative activity, bi-(AID-1-T) was shown to induce migration of recurrent tumor cells. This result shows the importance of studying the effect of therapeutic molecules on the invasive properties of glioma tumor cells in order to reduce the likelihood of inducing tumor recurrence. [ABSTRACT FROM AUTHOR]

Metastatic disease is a complex and sequential process that involves the migration of tumor cells from the primary site to distant areas. This metastatic pathway is not always predictable. Therefore, this paper presents three rare cases of unusual metastases, due to their primary site: two metastases of a clear cell renal cell carcinoma, one gingival, and one nasal, as well as a mandibular metastasis of a hepatocellular carcinoma. In all cases, an incisional biopsy was performed in order to find out the diagnosis. After microscopical examination of morphological Hematoxylin and Eosin-stained slides, for all cases, immunohistochemical reactions were performed to support the primary tumor site. Two cases had a previous histopathological diagnosis of a primary tumor, while for the third case, the metastatic lesion represented the first manifestation of the neoplastic disease, with an unfavorable prognosis. [ABSTRACT FROM AUTHOR]

YKL-40 is a secreted glycoprotein that can promote invasion, angiogenesis and inhibit apoptosis, and was highly expressed in a variety of tumours. In this paper, we investigated the impacts of YKL-40 on proliferation and invasion in HTR-8/SVneo cells during placenta accreta spectrum disorders (PAS) development. The levels of YKL-40 protein in late-pregnant placental tissue were detected using immunohistochemistry and Western blotting, and gene expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion and apoptosis abilities of HTR-8/SVneo cells were detected by cell counting kit-8 (CCK-8), Transwell, scratch assay, and flow cytometry, respectively. Our current results showed that YKL-40 was significantly increased in the PAS group compared to the normal control group (P < 0.01). Biological function experiments showed that YKL-40 significantly promoted the proliferation, migration and invasion of HTR-8/SVneo cells, and inhibited cell apoptosis. Knockdown of YKL-40 inhibited the activation of Akt/MMP9 signalling in trophoblast cells. These data suggested that YKL-40 might be involved in the progression of PAS, which may be attributed to the regulation of Akt/MMP9 signalling pathway. What is already known on this subject? YKL-40 is a secretory glycoprotein that can promote invasion, angiogenesis, and inhibit apoptosis and was highly expressed in a variety of tumours. Trophoblast cells resemble tumour cells in their migration and invasion. What the results of this study add? YKL-40 expression was significantly up-regulated in PAS. CCK-8 assays showed that YKL-40 remarkably enhanced the viability of HTR-8/SVneo cells. Scratch and Transwell assays demonstrated that YKL-40 significantly promoted the migration and invasion of HTR-8/SVneo cells. Additionally, YKL-40 attenuated apoptosis in HTR-8/SVneo cells. What the implications are of these findings for clinical practice and/or further research? Akt/MMP9 was involved in the regulation of YKL-40 on trophoblast invasion, which may provide theoretical basis and new ideas for the drug blocking intervention of placenta accreta. [ABSTRACT FROM AUTHOR]

This correction notice is for an article titled "Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration." The authors of the article discovered an error in Figure 6, where the images for siARC were incorrect and the same as the siZRANB images. The correct siARC images have now been included in the figure. The conclusions of the paper remain unaffected. The article provides a graph showing the effects of PMM depletion on cytoskeletal organization in HeLa cells. [Extracted from the article]

Malignant melanoma (MM) is a malignant tumor associated with high mortality rates and propensity for metastasis. Despite advancement in treatment, the incidence of MM continue to rise globally. GPR168, also known as MrgprF, is a MAS related GPR family member. The low expression of GPR168 has also been reported in many malignant tumors including MM. In the study, the statistical analysis from The Cancer Genome Atlas (TCGA) revealed a significant down regulation of GPR168 in melanoma compared to normal melanocytes, underscoring its importance in MM. The aim of the present study is to investigate the affect of GPR168 overexpression and elucidate its molecular mechanisms in MM cells. In addition, we used mouse melanoma B16-F10 cell line and xenograph tumor model to explore the function of GPR168 in melanoma. Our findings demonstrate that GPR168 overexpression could inhibit B16-F10 cell proliferation, migration, and xenografts tumor growth. Further, mechanistic studies revealed that GPR168 affected B16-F10 progress through Akt signal pathway with the decreased expression of p-Akt, p-GSK-3β, β-catenin, Myc, CyclinD1 and CDK4. In order to validate these findings, a rescue experiment was formulated employing GPR168 polyclonal antibody (Anti-GPR168 pAbs) to block GPR168 functionality. The addition of Anti-GPR168 pAbs into the culture medium restored both cell proliferation and migration. In conclusion, the overexpression of GPR168 in mouse melanoma B16-F10 cells suppressed proliferation and migration through the Akt signaling pathway. These findings collectively propose GPR168 as a promising novel tumor suppressor in MM, suggesting its potential as a therapeutic target in future interventions. [ABSTRACT FROM AUTHOR]

The treatment of osteosarcoma, as the most destructive bone cancer, is allied with many challenges. One of the new tissue engineering approaches is the use of a local drug delivery system implanted after surgery. This system can be a scaffold mimicking the natural tissue extracellular matrix, loaded with drugs. Therefore, the purpose of this study was to construct different berberine-loaded nano-hydroxyapatite/gelatin scaffolds, and to investigate their effects on osteosarcoma cancer cells. The scaffolds after fabrication were analyzed for physicochemical properties using XRD, EDS, FTIR, and FE-SEM. The drug loading and release, and the biocompatibility (MTT and LDH) were also evaluated. Moreover, apoptosis, viability, colony formation, and scratch tests were conducted on cancer cells. The scaffolds exhibited a porosity of 66.64% with pore sizes of 10–70 micrometers. The results showed that the released berberine had a cytotoxic effect on cancer cells (cell death of ∼38–80% based on LDH, and cell proliferation <56% and <21% in terms of early and late exposure based on MTT). The apoptosis results revealed a remarkable increase in the percentage of apoptotic MG63 cells after treatment with berberine-loaded scaffolds in a dose-dependent manner. All scaffolds with berberine were able to significantly prevent colony formation and cell migration (only 9.7–15.7% closure). [ABSTRACT FROM AUTHOR]

Cell shape plays a fundamental role in many biological processes, including adhesion, migration, division and development, but it is not clear which shape model best predicts three-dimensional cell shape in structured environments. Here, we compare different modelling approaches with experimental data. The shapes of single mesenchymal cells cultured in custom-made 3D scaffolds were compared by a Fourier method with surfaces that minimize area under the given adhesion and volume constraints. For the minimized surface model, we found marked differences to the experimentally observed cell shapes, which necessitated the use of more advanced shape models. We used different variants of the cellular Potts model, which effectively includes both surface and bulk contributions. The simulations revealed that the Hamiltonian with linear area energy outperformed the elastic area constraint in accurately modelling the 3D shapes of cells in structured environments. Explicit modelling the nucleus did not improve the accuracy of the simulated cell shapes. Overall, our work identifies effective methods for accurately modelling cellular shapes in complex environments. Author summary: Cell shape and forces have emerged as important determinants of cell function and thus their prediction is essential to describe and control the behaviour of cells in complex environments. While there exist well-established models for the two-dimensional shape of cells on flat substrates, it is less clear how cell shape should be modeled in three dimensions. Different from the philosophy of the vertex model often used for epithelial sheets, we find that models based only on cortical tension as a constant geometrical surface tension are not sufficient to describe the shape of single cells in 3D. Therefore, we employ different variants of the cellular Potts model, where either a target area is prescribed by an elastic constraint or the area energy is described with a linear surface tension. By comparing the simulated shapes to experimental images of cells in 3D scaffolds, we can identify parameters that accurately model 3D cell shape. [ABSTRACT FROM AUTHOR]

This paper shows for the first time that co-transplantation of human olfactory ensheathing cells with neurotrophin-3 into spinal cord cysts is more effective for activation of remyelination than transplantation of cells with brain-derived neurotrophic factor and a combination of these two factors. The studied neurotrophic factors do not affect proliferation and migration of ensheathing cells in vitro. It can be concluded that the maximum improvement of motor function in rats receiving ensheathing cells with neurotrophin-3 is largely determined by activation of remyelination. [ABSTRACT FROM AUTHOR]

Objective: Recently, the application in the field of germplasm resource conservation has become an important application of primordial germ cells (PGCs). However, due to the lack of deep understanding of the biological characteristics of PGCs at different time points, there is no systematic scheme for the selection of PGCs at which time points in practical application, which affects the practical application effect of PGCs. This study aims to clarify the differences in PGCs during development. Methods: Here, migration experiment, EdU proliferation assay and cell apoptosis assay were conducted to compare the differences in the migration ability, the proliferation ability and the recovery efficiency among female and male PGCs at E3.5, E4.5, and E5.5, which were explained by the following transcriptome sequencing analysis. Results: We found that there were larger differences between female and male PGCs at different embryonic ages, while smaller differences between female and male PGCs at the same embryonic age. Further comparison showed that the cell migration ability of female and male PGCs decreased gradually during development, so female and male PGCs at E3.5 are more suitable for in vitro allotransplantation. At the same time, the proliferation ability of PGCs gradually decreased during development, and cell adhesion and extracellular matrix communication were weakened, indicating that female and male PGCs of E3.5 are more suitable for in vitro long-term culture cell line establishment. Interestingly, female and male PGCs at E5.5 showed strong DNA damage repair ability, thus more suitable for in vitro long-term cryopreservation. Conclusion: This study provides a theoretical basis for systematically selecting PGCs at suitable developmental time points as cell materials for efficient utilization by analyzing the characteristics of female and male PGCs at different developmental time points based on transcriptome. [ABSTRACT FROM AUTHOR]

Purpose: Fibroblast activation protein (FAP) is highly expressed in the mesenchyme of most malignant epithelial tumors, while its expression is low in normal tissues. FAP inhibitors (FAPIs) bind specifically to FAP and are used for tumor-targeted diagnosis and therapy. The aim of this study was to radiosynthesize a novel molecular probe 131I-FAPI and evaluate its in-vitro targeting and biological characteristics. Methods: The structurally modified FAPI was labelled with 131I through the chloramine-T method. The radiolabeling rate was then detected by thin-layer chromatography (TLC). The stability of 131I-FAPI was determined at PBS (room temperature) and serum (37°C). Its hydrophilicity was calculated by measuring its lipid-water partition coefficient. Pancreatic cancer PANC-1 cell line and glioma U87 cell line were cultured in vitro. Cell uptake assay was used to show the binding ability of 131I-FAPI. The CCK-8 assay was used to calculate the inhibitory effects of 131I-FAPI at different time points (4h, 8h, 12h, 24h, 48h) after comparing with the 131I and FAPI. The before-and-after-24h scratch areas of the two cells were determined in order to verify the effect of 131I-FAPI on the migration ability of the cells. Results: The radiolabeling rate was (84.9 ± 1.02) %. The radiochemical purity of 131I-FAPI remained over 80% in both 25°C PBS and 37°C serum. The value of the lipid-water partition coefficient was -0.869 ± 0.025, indicating the hydrophilic of the probe. The cellular uptake assay showed that U87 cells had a specific binding capacity for 131I-FAPI. In cell inhibition assays, the inhibitory effect of 131I-FAPI on U87 cells increased with time. The results of cell scratch assay showed that 131IFAPI had the strongest inhibitory effect on the migratory ability of U87 cells compared with 131I and FAPI (P<0.001). Conclusion: 131I-FAPI was synthesized with good in-vitro stability and hydrophilic properties. It can be specifically bound by U87 cells. The proliferation and migration of U87 cells can be effectively inhibited. 131I-FAPI is promising to become a therapeutic probe. [ABSTRACT FROM AUTHOR]

The specificity of cytokine and immunoreceptor signaling frequently depends upon receptor recruitment of select adaptor proteins and specifically engaged effectors. This review focuses on the orthologous adaptor proteins, HGAL and C1ORF150, and aims to provide insight into their respective modulation of lymphoid and myeloid cell signaling, formation, and function. HGAL acts predominantly within germinal center B cells as an important BCR signal transducer. Effects on BCR signalosome assembly involve HGAL's localization to the plasma membrane via its lipidation, initial interactions with SYK, the pYphosphorylation of HGAL including its recruitment of GRB2, and HGAL engagement of PDZ-RhoGEF and RhoA signaling. At ligated BCRs, this includes HGAL(-GRB2) stimulation of SYK kinase, attenuation of calcium flux-dependent and NF-kB expression, promotion of cSMAC formation, and cytoskeletal remodeling associated with HGAL-attenuated cell migration. HGAL and partnered effectors also impact on DLBCL pathogenesis, and studies are summarized on HGAL's actions (using DLBCL and Burkitt lymphoma B cells) including cell migration effects, HGAL modulation of cytoskeletal components, and insightful HGAL transgenic mouse and xenograft models. For C1ORF150, its HGAL-homologous subdomains are considered, together with studies that demonstrate C1OR150's FceRI- and KIT-mediated expression and phosphorylation in primary human mast cells. Intriguingly, recent GWAS studies have identified a C1ORF150 in-frame splice variant that is strongly associated with urticaria. Candidate mechanisms via which the encoded "C1ORF150-Dexon2" isoform affects mast cell degranulation are considered, including FceR1 and/or KIT receptor connections, and candidate "myristoylation switch" mechanisms. [ABSTRACT FROM AUTHOR]

Background: The influence of the small Rho GTPase Rif (RHOF) on tumor growth, glycolysis, endothelial–mesenchymal transition (EMT), and the potential mechanism of RHOF in pancreatic cancer (PC) were explored. Methods: RHOF expression in PC tissues and cells was assessed by qRT-PCR and western blotting. The viability, proliferation, apoptosis, migration, and invasion of PC cells were assessed using CCK-8, colony formation, EdU, flow cytometry, scratch, and Transwell assays. The expression of EMT- and glycolysis-related proteins was determined using western blotting. The potential mechanisms of action of RHOF in PC were identified using bioinformatic analysis. The effects of RHOF were assessed in vivo using a xenograft mouse model. Results: PC cell proliferation, migration, and invasion are accelerated by RHOF overexpression, which inhibited apoptosis. RHOF overexpression promoted EMT and glycolysis as evidenced by a decrease in E-cadherin expression and an increase in N-cadherin, Vimentin, HK2, PKM2, and LDHA expression. Bioinformatic analysis indicated that RHOF activated EMT, glycolysis, and Myc targets and that c-Myc could bind to the PKM2 promoter. RHOF overexpression promotes the lactylation and nuclear translocation of Snail1. Silencing Snail1 reversed the promoting effects of RHOF and lactate on cell migration, invasion, and EMT. Moreover, in vivo tumor growth and EMT were inhibited by RHOF silencing. Conclusion: RHOF plays an oncogenic role in PC. c-Myc is upregulated by RHOF and promotes PKM2 transcription. PKM2 further induces glycolysis, and the lactate produced by glycolysis causes the lactylation of Snail1, ultimately promoting EMT. [ABSTRACT FROM AUTHOR]

Collective migration of eukaryotic cells is often guided by chemotaxis, and is critical in several biological processes, such as cancer metastasis, wound healing, and embryogenesis. Understanding collective chemotaxis has challenged experimental, theoretical and computational scientists because cells can sense very small chemoattractant gradients that are tightly controlled by cell-cell interactions and the regulation of the chemoattractant distribution by the cells. Computational models of collective cell migration that offer a high-fidelity resolution of the cell motion and chemoattractant dynamics in the extracellular space have been limited to a small number of cells. Here, we present Dynamic cluster field modeling (DCF), a novel computational method that enables simulations of collective chemotaxis of cellular systems with O (1000) cells and high-resolution transport dynamics of the chemoattractant in the time-evolving extracellular space. We illustrate the efficiency and predictive capabilities of our approach by comparing our numerical simulations with experiments in multiple scenarios that involve chemoattractant secretion and uptake by the migrating cells, cell migration in confined spaces, regulation of the attractant distribution by cell motion, and interactions of the chemoattractant with an enzyme. The proposed algorithm opens new opportunities to address outstanding problems that involve collective cell migration in the central nervous system, immune response and cancer metastasis. [ABSTRACT FROM AUTHOR]

Ponicidin is a diterpenoid with demonstrated antitumor activity in clinical trials. However, the specific function and mechanism of action against hepatocellular carcinoma (HCC) remain unknown. In this study, it is found that ponicidin significantly inhibited the proliferation and migration of HCC cells. It is shown that ponicidin targets Keap1 and promotes the formation of the Keap1‐PGAM5 complex, leading to the ubiquitination of PGAM5, using biotin‐labeled ponicidin for target fishing and the HuProtTM Human Proteome Microarray V4.0. Ponicidin is found to activate the cysteine‐dependent mitochondrial pathway via PGAM5, resulting in mitochondrial damage and ROS production, thereby promoting mitochondrial apoptosis in HepG2 cells. The first in vitro cocrystal structure of the PGAM5 IE 12‐mer peptide and the Keap1 Kelch domain is obtained. Using molecular dynamics simulations to confirm the binding of ponicidin to the Keap1‐PGAM5 complex. Based on the depth‐based dynamic simulation, it is found that ponicidin can induce the tightening of the Keap1‐PGAM5 interaction pocket, thereby stabilizing the formation of the protein complex. Finally, it is observed that ponicidin effectively inhibited tumor growth and promoted tumor cell apoptosis in a BALB/c nude mouse xenograft tumor model. The results provide insight into the anti‐HCC properties of ponicidin based on a mechanism involving the Keap1‐PGAM5 complex. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a leading cause of cardiovascular diseases, characterized by endothelial dysfunction and lipid accumulation. Long non-coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell behavior. This study aimed to investigate the role of lncRNA NORAD in endothelial cell proliferation and as a potential therapeutic target for atherosclerosis. A total of 75 CAD patients and 76 controls were recruited, and plasma NORAD levels were measured using qRT-PCR. HUVECs were transfected with si-NORAD to evaluate its effects on cell cycle, proliferation, migration, and apoptosis. Plasma NORAD levels were significantly elevated in CAD patients. The NORAD-miRNA-mRNA ceRNA regulatory network was constructed based on GEO database, and G1/S-specific cyclin-D1 (CCND1) was identified as one of the hub factors. NORAD deficiency suppressed cell migration and induced G1 cell cycle arrest in HUVECs by downregulating CCND1 in vitro. NORAD upregulated CCND1 in HUVECs via sponging miR-106a that inhibited cell migration. The dual-luciferase assay confirmed the direct targeting of miR-106a by NORAD, and overexpression of miR-106a inhibited HUVEC proliferation and migration. Si-NORAD transfection resulted in induced early apoptosis, increased intracellular ROS levels, decreased GSH levels, and reduced mitochondrial membrane potential. Additionally, si-NORAD decreased the expression of GPX4, FTH1, KEAP1, NCOA4, and Nrf2, while increasing Xct levels, confirming the involvement of ferroptosis. Our findings reveal that NORAD plays a critical role in endothelial cell proliferation, migration, and apoptosis, and its silencing induces ferroptosis. The regulatory network involving NORAD, miR-106a, and their target genes provides a potential therapeutic avenue for atherosclerosis. [ABSTRACT FROM AUTHOR]

The serine/threonine/tyrosine kinase 1 (STYK1) is a receptor protein-tyrosine kinase (RPTK)-like molecule that is detected in several human organs. STYK1 plays an important role in promoting tumorigenesis and metastasis in various cancers. By analyzing the expression of RTKs in immune cells in the database of 2013 Immunological Genome Project, we found that STYK1 was principally expressed in NK cells. In order to investigate the function of STYK1, we used CRISPR/Cas9 technology to generate STYK1-deleted mice, we found STYK1 deletion mice have normal number, development, and function of NK cells in spleen and bone marrow in tumor-free resting state. To examine the tumor surveillance of STYK1 in vivo, we utilized a variety of tumor models, including NK cell-specific target cell (ß2M and RMA-S) clearance experiments in vivo, subcutaneous and intravenous injection of B16F10 melanoma model, and the spontaneous breast cancer model MMTV-PyMT. Surprisingly, we discovered that deletion of the oncogenic STYK1 promoted the four-model tumor progression, and we observed a reduction of NK cell accumulation in the tumor tissues of STYK1 deletion mice compared to WT mice. In order to study the mechanism of STYK1 in NK, RNA sequence of STYK1−/− and WT NK have unveiled a disparity in the signaling pathways linked to migration and adhesion in STYK1−/− NK cells. Further analysis of chemokine receptors associated with NK cell migration revealed that STYK1-deficient NK cells exhibited a significant reduction in CCR2 expression. The STYK1 expression was negatively associated with tumor progression in glioma patients. Overall, our study found the expression of STYK1 in NK cell mediates NK cell anti-tumor response through regulating CCR2 and infiltrating into tumor tissue. [ABSTRACT FROM AUTHOR]

Background: Lipid metabolism dysregulation is a key characteristic of hepatocellular carcinoma (HCC) onset and progression. Elevated expression of immunoglobulin (Ig), especially the Igκ free light chain with a unique Vκ4-1/Jκ3 rearrangement in cancer cells, is linked to increased malignancy and has been implicated in colon cancer tumorigenesis. However, the role of Igκ in HCC carcinogenesis remains unclear. The aim of this study was to elucidate the pivotal roles of hepatocyte-derived Igκ in HCC development. Methods: The rearrangement sequence and expression level of hepatocyte-derived Igκ in HCC cells were determined via RT-PCR, Sanger sequencing, immunohistochemistry, and western blot analysis. The function of Igκ in HCC tumorigenesis was assessed by silencing Igκ using siRNA or gRNA in various HCC cell lines. To assess the role of Igκ in HCC pathogenesis in vivo, a mouse model with hepatocyte-specific Igκ knockout and diethylnitrosamine (DEN) and carbon tetrachloride (CCL4)-induced HCC was utilized. The molecular mechanism by which Igκ affects HCC tumorigenesis was investigated through multiomics analyses, quantitative real-time PCR, immunoprecipitation, mass spectrometry, immunofluorescence, and metabolite detection. Results: We confirmed that Igκ, especially Vκ4-1/Jκ3-Igκ, is highly expressed in human HCC cells. Igκ depletion inhibited HCC cell proliferation and migration in vitro, and hepatocyte-specific Igκ deficiency ameliorated HCC progression in mice with DEN and CCL4-induced HCC in vivo. Mechanistically, Vκ4-1/Jκ3-Igκ interacts with electron transfer flavoprotein subunit α (ETFA), delaying its protein degradation. Loss of Igκ led to a decrease in the expression of mitochondrial respiratory chain complexes III and IV, resulting in aberrant fatty acid β-oxidation (FAO) and lipid accumulation, which in turn inhibited HCC cell proliferation and migration. Conclusion: Our findings indicate that the Igκ/ETFA axis deregulates fatty acid β-oxidation, contributing to HCC progression, which suggests that targeting fatty acid metabolism may be an effective HCC treatment strategy. The results of this study suggest that hepatocyte-derived Vκ4-1/Jκ3-Igκ may serve as a promising therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is a highly chemoresistant malignancy with a poor prognosis. Paclitaxel's low response rate as second-line chemotherapy for advanced GC has prompted intensive research into its molecular basis and prospective targeted therapies to enhance its therapeutic efficacy. The objective of this study was to investigate the synergistic effects of NRF2 silencing in combination with paclitaxel treatment on GC cell viability, apoptosis, proliferation, autophagy, and migration. Methods: \After the siRNA-mediated silencing of NRF2 in AGS cells, the transfection efficacy was evaluated by qRT-PCR. The MTT assay was then applied to assess cell viability, followed by flow cytometry analysis for apoptosis, proliferation, and autophagy in AGS cells treated with NRF2 siRNA, paclitaxel, or their combination. Thereafter, the migration of cells was measured using a wound-healing assay. Ultimately, the relative gene expression levels of apoptotic (Bax, Caspase-3, and Caspase-9), anti-apoptotic (Bcl-2), metastatic (MMP-2), and cell cycle (P53) genes were measured by qRT-PCR in all experiment groups to further assess the molecular basis for the combination therapy. Results: NRF2 siRNA transfection significantly enhanced paclitaxel-induced apoptosis and sensitized AGS cells to paclitaxel via modulating the expression of apoptosis-related genes including Bcl-2, Bax, Caspase-3, and Caspase-9. Besides, NRF2 siRNA and paclitaxel synergistically induced cell cycle arrest at the G2 phase, promoted autophagy activation, and inhibited AGS cell migration via MMP-2 downregulation. Additionally, P53, a key regulator of cell growth, was significantly upregulated in the treated groups compared to the control group. Conclusions: Our findings suggest that paclitaxel combined with siRNA-mediated silencing of NRF2 might represent a promising therapeutic strategy for GC, however further translational and clinical research are warranted. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) ranks as the fifth most prevalent cancer globally, and its pronounced invasiveness and propensity to spread provide significant challenges for therapy. At present, there are no efficacious medications available for the treatment of patients with GC. Isoliensinine (ISO), a bisbenzylisoquinoline alkaloid, was isolated from Nelumbo nucifera Gaertn. It possesses anti-tumor, antioxidant, and other physiological effects. Nevertheless, there is currently no available study on the impact of ISO on GC, and further investigation is needed to understand its molecular mechanism. Methods: ISO target points and GC-related genes were identified, and the crosstarget points of ISO and GC were obtained. We then examined cross-targeting and found genes that were differentially expressed in GCs. Kaplan-Meier survival curves were used to screen target genes, and the STRING database and Cytoscape 3.9.1 were used to construct protein-protein interactions and drug-target networks. In addition, molecular docking studies confirmed the interactions between ISO screen targets. Finally, in vitro tests were used to establish the impact of ISO on GC cells. Results: Through bioinformatics research, we have identified TGFBR1 as the target of ISO in GC. In addition, we noticed a substantial inhibition in GC cell proliferation, migration, and invasion activities following ISO treatment. Moreover, we noticed that ISO treatment effectively suppressed TGF-ß-induced epithelial-mesenchymal transition (EMT) and activation of the TGF-ß-Smad pathway. Furthermore, we discovered that siTGFBR1 nullified the impact of ISO on TGF-ß-triggered migration, invasion, and activation of the TGF-ß-Smad pathway. Conclusion: Our research suggests that ISO specifically targets TGFBR1 and regulates the TGF-ß-Smad signaling pathway to suppress the proliferation and migration of GC cells. [ABSTRACT FROM AUTHOR]

This research investigates the intricate involvement of nuclear Transcription Factor Y Subunit Alpha (NFYA) in the advancement of castration-resistant prostate cancer (CRPC) and its consequential impact on early Growth Response 4 (EGR4) expression. NFYA demonstrates a significant elevation in CRPC tissues and cell lines, displaying robust upregulation in metastatic prostate cancer (mPCa) samples, closely associated with the Gleason score. Immunohistochemistry validates heightened nuclear staining of NFYA in CRPC patients, highlighting its crucial role in the progression of advanced prostate cancer. Silencing NFYA through siRNA in androgen-independent cell lines markedly impedes cell growth and migration, emphasizing NFYA's pivotal role in promoting CRPC behavior. RNA-seq analysis identifies EGR4 as a downstream target of NFYA, with both genes consistently upregulated in CRPC. Validating this finding, heightened expression of EGR4 is observed in CRPC samples. In vivo studies utilizing a mouse model demonstrate that NFYA silencing substantially inhibits LNCaP-AI/22RV1shNFYA xenograft tumor growth, accompanied by reduced expression of EGR4 and Ki67. This comprehensive study reveals the multifaceted role of NFYA in CRPC progression, elucidates its downstream impact on EGR4, and underscores the therapeutic potential of targeting NFYA to inhibit CRPC growth in vivo. These findings contribute valuable insights into potential therapeutic strategies for managing CRPC. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to investigate the potential anti-cancer effects of Micromeria fruticosa plant infusion on uterine cervix cancer cells, aiming to explore its potential as an alternative or supportive therapeutic approach to conventional treatments. Methods: Micromeria fruticosa plant infusion was prepared and administered to uterine cervix cancer cells in vitro. Various assays were conducted to assess its impact on cell migration, proliferation, and tumorigenicity. Additionally, the phytochemical composition of the infusion was analyzed by using LC-MS to identify major functional compounds. Results: The study revealed that Micromeria fruticosa plant infusion exhibited significant anti-migratory, anti-proliferative, and anti-tumorigenic effects on uterine cervix cancer cells. Analysis of the infusion identified several major functional phytochemicals, which likely contribute to its anticancer properties. Conclusion: This research suggests that Micromeria fruticosa plant infusion possesses promising anti-cancer properties against uterine cervix cancer cells. The identified phytochemicals present in the infusion highlight its potential as a source of functional ingredients with anticancer effects. These findings support further exploration of Micromeria fruticosa as a potential therapeutic agent in both nutraceutical and pharmaceutical applications, offering new avenues for the development of alternative or supportive treatments for cervical cancer. [ABSTRACT FROM AUTHOR]

Understanding the niche interactions between blood and bone through the in vitro co-culture of osteo-competent cells and endothelial cells is a key factor in unraveling therapeutic potentials in bone regeneration. This can be additionally supported by employing numerical simulation techniques to assess local physical factors, such as oxygen concentration, and mechanical stimuli, such as shear stress, that can mediate cellular communication. In this study, we developed a Mesenchymal Stem Cell line (MSC) and a Human Umbilical Vein Endothelial Cell line (HUVEC), which were co-cultured under flow conditions in a three-dimensional, porous, natural pullulan/dextran scaffold that was supplemented with hydroxyapatite crystals that allowed for the spontaneous formation of spheroids. After 2 weeks, their viability was higher under the dynamic conditions (>94%) than the static conditions (<75%), with dead cells central in the spheroids. Mineralization and collagen IV production increased under the dynamic conditions, correlating with osteogenesis and vasculogenesis. The endothelial cells clustered at the spheroidal core by day 7. Proliferation doubled in the dynamic conditions, especially at the scaffold peripheries. Lattice Boltzmann simulations showed negligible wall shear stress in the hydrogel pores but highlighted highly oxygenated zones coinciding with cell proliferation. A strong oxygen gradient likely influenced endothelial migration and cell distribution. Hypoxia was minimal, explaining high viability and spheroid maturation in the dynamic conditions. [ABSTRACT FROM AUTHOR]

(1) Background: Methyl jasmonate-treated D. morbifera adventitious root extract (MeJA-DMARE), enriched with phenolics, has enhanced bioactivities. However, phenolics possess low stability and bioavailability. Substantial evidence indicates that plant extract–phospholipid complex assemblies, known as phytosomes, represent an innovative drug delivery system. (2) Methods: The phytosome complex was created by combining MeJA-DMARE with Soy-L-α-phosphatidylcholine (PC) using three different ratios through two distinct methods (co-solvency method: A1, A2, and A3; thin-layer film method: B1, B2, and B3). (3) Results: Initial evaluation based on UV-Vis, entrapment efficiency (EE%), and loading content (LC%) indicated that B2 exhibited the highest EE% (79.98 ± 1.45) and LC% (69.17 ± 0.14). The phytosome displayed a spherical morphology with a particle size of 210 nm, a notably low polydispersity index of 0.16, and a superior zeta potential value at −25.19 mV. The synthesized phytosome exhibited superior anti-inflammatory activities by inhibiting NO and ROS production (reduced to 8.9% and 55.1% at 250 μg/mL) in RAW cells and adjusting the expression of related inflammatory cytokines; they also slowed lung tumor cell migration (only 2.3% of A549 cells migrated after treatment with phytosomes at 250 μg/mL), promoting ROS generation in A549 cell lines (123.7% compared to control) and stimulating apoptosis of lung cancer-related genes. (4) Conclusions: In conclusion, the MeJA-DMARE phytosome offers stable, economically efficient, and environmentally friendly nanoparticles with superior inflammation and lung tumor inhibition properties. Thus, the MeJA-DMARE phytosome holds promise as an applicable and favorable creation for drug delivery and lung cancer treatment. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and drug resistance and no targeted drug available at present. Compound 4, a staurosporine alkaloid derived from Streptomyces sp. NBU3142 in a marine sponge, exhibits potent anti-TNBC activity. This research investigated its impact on MDA-MB-231 cells and their drug-resistant variants. The findings highlighted that compound 4 inhibits breast cancer cell migration, induces apoptosis, arrests the cell cycle, and promotes cellular senescence in both regular and paclitaxel-resistant MDA-MB-231 cells. Additionally, this study identified mitogen-activated protein kinase kinase kinase 11 (MAP3K11) as a target of compound 4, implicating its role in breast tumorigenesis by affecting cell proliferation, migration, and cell cycle progression. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is the 8th most common cancer among women overall. Licorice contains over 300 active compounds, many of them with anti-cancer properties. Glycyrrhetinic acid (GA) is a major component of licorice. The aim of this study was to investigate the potential anti-proliferative effects of licorice and GA on PTC cell cultures. Licorice extract (LE) was produced from the root and tested on BCPAP and K1 cell lines, as well as GA and aldosterone. We used the MTT test to investigate the anti-proliferative activity, the wound healing test for the migratory activity, and finally, we analyzed cell cycle distribution, apoptosis, and oxidative stress after LE, GA, or aldosterone incubation. Both LE and GA reduced cell viability at 48 h and cell migration at 24 h in both PTC cultures. Aldosterone reduced cell migration only in K1 cells. LE and GA induced cell cycle arrest in the G0/G1 phase in the BCPAP cell line, while LE and aldosterone induced it in the K1 culture. GA but not LE increased the apoptosis rate in both cell lines, whereas LE but not GA increased oxidative stress in both cultures. This study presents the first evidence of the in vitro anti-proliferative and anti-migratory activity of LE and GA on PTC. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a long-term autoimmune condition marked by persistent inflammation of the joints and various systemic complications, including endothelial dysfunction, atherosclerosis, and pulmonary fibrosis. Oxidative stress is a key contributor to the pathogenesis of RA, potentially exacerbating vascular damage and promoting pro-angiogenic and profibrotic processes. Objective: This study aims to investigate the effects of sera from RA patients on human umbilical vein endothelial cells (HUVECs), focusing on the induction of oxidative stress, endothelial cell proliferation, migration, and collagen type I synthesis. Methods: Twenty-eight serum samples were collected from RA patients and healthy donors (HDs). HUVECs were exposed to these sera, and intracellular reactive oxygen species (ROS) levels were fluorescently detected using H2DCF-DA. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell migration was evaluated through a scratch wound assay, and collagen type I synthesis was measured using a lentiviral vector expressing the green fluorescent protein (GFP) under the control of the human COL1A1 gene promoter. Results: Exposure to RA sera resulted in a significant increase in intracellular ROS levels in HUVECs compared to HD sera, indicating an elevated state of oxidative stress. RA sera also promoted endothelial cell proliferation and migration, suggesting a pro-angiogenic stimulus. Additionally, RA sera significantly increased collagen type I synthesis in HUVECs, implicating a potential role in profibrotic processes associated with RA. Conclusion: The results of this study emphasize the importance of circulating factors in RA sera in promoting oxidative stress, endothelial dysfunction, and pro-angiogenic and profibrotic phenotypes in endothelial cells. These processes may contribute to the vascular and fibrotic complications observed in RA, highlighting the necessity for additional research into focused therapeutic approaches to alleviate these effects. [ABSTRACT FROM AUTHOR]

To improve the utilization of by-products of the Hyriopsis cumingii, this study investigated the effect of Hyriopsis cumingii polysaccharide (HCP) on the proliferation and migration of normal cells, as well as its reparative effects on ultraviolet radiation-B (UVB)-damaged cells. First, HCP was isolated and purified using DEAE Cellulose-52 column chromatography, Sephadex G-100 column chromatography and nanofiltration. Then, structural analysis was conducted using high-performance liquid chromatography, high-performance gel permeation chromatography, and infrared spectroscopy. Following this, cell proliferation experiments, cell scratch tests, UVB damage experiments, and protein expression analyses were employed to explore the anti-UVB damage effects and corresponding mechanisms of polysaccharide components. The results indicated the three substances obtained by isolation and purification were all homogeneous polysaccharide components. Among them, HCP-2 played a major role in promoting cell proliferation in HCP and facilitated the migration of HaCaT cells. The recovery of UVB-damaged cell vitality was raised by the increasing concentration of HCP-2. Furthermore, the reparative effect was more substantial than the protective effect at the same sample concentration. It was also observed that HCP-2 up-regulated the expression of the anti-apoptotic protein bcl-2 while inhibited the expression of apoptosis-related proteins casp9, p-Akt, and p-p38, indicating that HCP-2 could repair HaCaT cells by regulating apoptosis of cells damaged by UVB. In conclusion, HCP had the ability to inhibit cell apoptosis which provide a theoretical basis for its future application in the development of food and health products. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is a global malignancy characterized by metastatic invasiveness and recurrence. Long non-coding RNAs (lncRNAs) and Telomeres are closely connected with several cancers, but their potential as practical prognostic markers in OC is less well-defined. Methods: Relevant mRNA and clinical data for OC were sourced from The Cancer Genome Atlas (TCGA) database. The telomere-related lncRNAs (TRLs) prognostic model was established by univariate/LASSO/multivariate regression analyses. The effectiveness of the TRLs model was evaluated and measured via the nomogram. Additionally, immune infiltration, tumor mutational load (TMB), and drug sensitivity were evaluated. We validated the expression levels of prognostic genes. Subsequently, PTPRD-AS1 knockdown was utilized to perform the CCK8 assay, colony formation assay, transwell assay, and wound healing assay of CAOV3 cells. Results: A six-TRLs prognostic model (PTPRD-AS1, SPAG5-AS1, CHRM3-AS2, AC074286.1, FAM27E3, and AC018647.3) was established, which can effectively predict patient survival rates and was successfully validated using external datasets. According to the nomogram, the model could effectively predict prognosis. Furthermore, we detected the levels of regulatory T cells and M2 macrophages were comparatively higher in the high-risk TRLs group, but the levels of activated CD8 T cells and monocytes were the opposite. Finally, the low-risk group was more sensitive to anti-cancer drugs. The mRNA levels of PTPRD-AS1, SPAG5-AS1, FAM27E3, and AC018647.3 were significantly over-expressed in OC cell lines (SKOV3, A2780, CAOV3) in comparison to normal IOSE-80 cells. AC074286.1 were over-expressed in A2780 and CAOV3 cells and CHRM3-AS2 only in A2780 cells. PTPRD-AS1 knockdown decreased the proliferation, cloning, and migration of CAOV3 cells. Conclusion: Our study identified potential biomarkers for the six-TRLs model related to the prognosis of OC. [ABSTRACT FROM AUTHOR]