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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]

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]

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]

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]

Atractylodin is one of the main active ingredients of Atractylodis Rhizoma. It has various pharmacological properties, such as antigastric ulcer, immune regulation, antibacterial, anti-inflammatory, antitumor, anti-oxidant, and neuroprotective properties. In the past few decades, atractylodin has attracted the attention of researchers due to its excellent therapeutic effects. This paper aims to review the pharmacology of atractylodin, focusing mainly on its pharmacological effects in tumor treatment. Atractylodin exerts its antitumor effect by regulating different signaling pathways to induce important biological events such as apoptosis, cell cycle arrest, and autophagy, inhibiting cancer cell invasion and metastasis. In the process of cell apoptosis, atractylodin mainly induces cancer cell apoptosis by downregulating the Notch signaling pathway, affecting multiple upstream and downstream targets. In addition, atractylodin induces autophagy in cancer cells by regulating various signaling pathways such as PI3K/AKT/mTOR, p38MAPK, and hypothalamic Sirt1 and p-AMPK. Atractylodin effectively induces G1/M and G2/M phase arrest under the action of multiple signaling pathways. Among them, the pathways related to G1/M are more widely stagnated. In inhibiting the migration and invasion of cancer cells, atractylodin mainly regulates the Wnt signaling pathway, downregulates the expression of N-cadherin in cancer cells, and then blocks the PI3K/AKT/mTOR signaling pathway, inhibiting the phosphorylation of PI3K, AKT, and mTOR proteins, thereby having a significant impact on the invasion and migration of cancer cells. This paper systematically reviews the research progress on the antitumor effects and mechanisms of atractylodin, hoping to provide a reference and theoretical basis for its clinical application and new drug development. [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]

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]

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]

Cellular migration is the movement of cells, cultured as a monolayer; cellular invasion is similar to migration, but requires the cells to move through a three-dimensional material such as basement membrane extract or a synthetic hydrogel. Migration assays, such as the transwell assay, are widely used to study cellular movement because they are amenable to high-throughput screens with minimal experimental setup. These assays offer limited information about cellular responses to gradients in vivo because they oversimplify the threedimensional (3D) environment of a tissue. There are a number of invasion assays that support 3D cultures, some of which provide experimental control over the spatial and temporal gradients imparted on the culture. These assays, in their current form, are difficult to setup and maintain, and often require specialized laboratory equipment or engineering expertise. Here we describe a paper-based invasion assay in which cellular movement can be monitored in real-time with fluorescence microscopy. These assays are easily prepared and utilize materials commonly found in any laboratory: a single sheet of paper. These sheets are wax patterned to contain channels in which cells suspended in a hydrogel are seeded and cultured. Cell-containing sheets of paper are placed in a custom-built holder that allows gradients to form along the length of the channels. In this work, we compare the invasion of cells cultured in the presence and absence of an oxygen gradient. Our result support previous findings that oxygen is a chemoattractant, and selectively directs cellular movement in a 3D culture environment. [ABSTRACT FROM AUTHOR]

This work demonstrates the application of a 3D culture system— C ells- i n- G els- i n- P aper (CiGiP)—in evaluating the metabolic response of lung cancer cells to ionizing radiation. The 3D tissue-like construct—prepared by stacking multiple sheets of paper containing cell-embedded hydrogels—generates a gradient of oxygen and nutrients that decreases monotonically in the stack. Separating the layers of the stack after exposure enabled analysis of the cellular response to radiation as a function of oxygen and nutrient availability; this availability is dictated by the distance between the cells and the source of oxygenated medium. As the distance between the cells and source of oxygenated media increased, cells show increased levels of hypoxia-inducible factor 1-alpha, decreased proliferation, and reduced sensitivity to ionizing radiation. Each of these cellular responses are characteristic of cancer cells observed in solid tumors. With this setup we were able to differentiate three isogenic variants of A549 cells based on their metabolic radiosensitivity; these three variants have known differences in their metastatic behavior in vivo . This system can, therefore, capture some aspects of radiosensitivity of populations of cancer cells related to mass-transport phenomenon, carry out systematic studies of radiation response in vitro that decouple effects from migration and proliferation of cells, and regulate the exposure of oxygen to subpopulations of cells in a tissue-like construct either before or after irradiation. [ABSTRACT FROM AUTHOR]

A simple method is described for the patterned deposition of Teflon on paper to create an integrated platform for parallel organic synthesis and cell-based assays. Solvent-repelling barriers made of Teflon-impregnated paper confine organic solvents to specific zones of the patterned array and allow for 96 parallel flow-through syntheses on paper. The confinement and flow-through mixing significantly improves the peptide yield and simplifies the automation of this synthesis. The synthesis of 100 peptides ranging from 7 to 14 amino acids in length gave over 60 % purity for the majority of the peptides (>95 % yield per coupling/deprotection cycle). The resulting peptide arrays were used in cell-based screening to identify 14 potent bioactive peptides that support the adhesion or proliferation of breast cancer cells in a 3D environment. In the future, this technology could be used for the screening of more complex phenotypic responses, such as cell migration or differentiation. [ABSTRACT FROM AUTHOR]

Microfluidic chemotaxis platforms have historically been utilized to probe phenomena such as neutrophil migration and are beginning to be developed for diagnostic applications; however, current microfluidic chemotaxis systems require specialized engineering equipment such as syringe pumps and long time frames (hours) to develop a chemokine gradient, and cell chemotaxis typically requires multiple additional hours. The paperfluidic device described in this work is a low-cost, sharp (2 mm wide), quasi-stable (at least 20 min) and rapidly generated (<1 s) chemokine gradient system capable of examining cell migration response over short time frames (20 min) that can be easily assembled. A proof-of-concept experiment on human pan-T cells showed significant (p ≪ 0.01) directed migration to the chemokine gradient over the control condition. This new technique for cell migration studies provides a foundational step in designing microfluidic chemotactic platforms for point-of-care diagnostics. [ABSTRACT FROM AUTHOR]

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]

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]

Hyaluronic acid (HA), as one of the main components of the extracellular matrix (ECM), plays an important role in the process of wound-healing and tissue-repair processes due to its unique properties and different physiological functions. HA has an ability to maintain a moist environment that promotes healing, the stimulation of growth factors and cellular constituents, and the migration of various cells essential for healing. This paper offers a review of HA use in the process of wound healing, with emphasis on hard-to-heal wounds, and examines its various applications in ophthalmology and otorhinolaryngology. It proves HA to be a versatile agent which finds its use in various fields of medicine for its antioxidant, anti-inflammatory, antibacterial properties and accelerated wound healing. [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]

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]

In vitro 3D culture is an important model for tissues in vivo. Cells in different locations of 3D tissues are physiologically different, because they are exposed to different concentrations of oxygen, nutrients, and signaling molecules, and to other environmental factors (temperature, mechanical stress, etc). The majority of high-throughput assays based on 3D cultures, however, can only detect the average behavior of cells in the whole 3D construct. Isolation of cells from specific regions of 3D cultures is possible, but relies on low-throughput techniques such as tissue sectioning and micromanipulation. Based on a procedure reported previously ("cells-in-gels-in-paper" or CiGiP), this paper describes a simple method for culture of arrays of thin planar sections of tissues, either alone or stacked to create more complex 3D tissue structures. This procedure starts with sheets of paper patterned with hydrophobic regions that form 96 hydrophilic zones. Serial spotting of cells suspended in extracellular matrix (ECM) gel onto the patterned paper creates an array of 200 micron-thick slabs of ECM gel (supported mechanically by cellulose fibers) containing cells. Stacking the sheets with zones aligned on top of one another assembles 96 3D multilayer constructs. De-stacking the layers of the 3D culture, by peeling apart the sheets of paper, "sections" all 96 cultures at once. It is, thus, simple to isolate 200-micron-thick cell-containing slabs from each 3D culture in the 96-zone array. Because the 3D cultures are assembled from multiple layers, the number of cells plated initially in each layer determines the spatial distribution of cells in the stacked 3D cultures. This capability made it possible to compare the growth of 3D tumor models of different spatial composition, and to examine the migration of cells in these structures. [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]

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]

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]

Chemical byproducts produced by surrounding industrial complexes have polluted the local estuaries of Georgetown, South Carolina for several decades1. Previous studies completed by the EPA and SCDNR showed that the estuaries contained carcinogenic pollutants released from the local manufacturing plants1. One of the mentioned pollutants was dioxins which are produced during the paper bleaching process2. Dioxins are highly toxic compounds that have various carcinogenic effects on the organisms that inhabit the area. These previous studies were conducted over thirty years ago. Therefore, a current study to determine if chemical byproducts are contaminating local estuaries is crucial in determining if companies are abiding by the limits set by the EPA. To complete this experiment, water was collected from Sampit River and filtered through vacuum filtration. The collected water was added to media in a Boyden chamber assay containing neuroblasts in order to observe cell migration. qPCR was completed to analyze ID2, which was utilized as a biomarker for possible tumorigenic expression within the neuroblasts. Large populations of the neuroblasts in the Boyden chamber with the same starting seeding density in control vs experimental samples resulted in increased migration. In further spontaneous motility assays, tumor-like aggregated morphologies formed, showing that carcinogens are possibly present in experimental samples that are leading to oncogenic effects. qPCR analysis showed increased ID2 expression in the neuroblasts, which is a biomarker of tumorigenicity in the neuroblasts. These results indicated that chemical byproducts could be in the local watersheds of Georgetown, South Carolina. [ABSTRACT FROM AUTHOR]

Severe fracture non-union often accompanied by damaged or even absent periosteum remains a significant challenge. This paper presents a novel tri-layer bionic periosteum with gradient structure and mineralized collagen (MC) mimics natural periosteum for in-situ repair and bone regeneration. The construct with ultrasonic polylactic acid as the loose outer fibrous layer (UPLA), poly(ε-caprolactone) as the intermediate barrier layer (PCL-M), and poly(ε-caprolactone)/MC as the inner osteoblastic layer (PM) was prepared. The physicochemical properties of layers were investigated. UPLA/PCL-M/PM exhibited a tensile strength (3.55 ± 0.23 MPa) close to that of natural periosteum and excellent adhesion between the layers. In vitro experiments demonstrated that all layers had no toxicity to cells. UPLA promoted inward growth of mouse fibroblasts. PCL-M with a uniform pore size (2.82 ± 0.05 μm) could achieve a barrier effect against fibroblasts according to the live/dead assay. Meanwhile, PM could effectively promote cell migration with high alkaline phosphatase expression and significant mineralization of the extracellular matrix. Besides, in vivo experiments showed that UPLA/PCL-M/PM significantly promoted the regeneration of bone and early angiogenesis. Therefore, this construct with gradient structure developed in this paper would have great application potential in the efficient and high-quality treatment of severe fractures with periosteal defects. [Display omitted] [ABSTRACT FROM AUTHOR]

The present work extends a previous paper where an agent-based and two-dimensional partial differential diffusion model was introduced for describing immune cell dynamics (leukocytes) in cancer-on-chip experiments. In the present work, new features are introduced for the dynamics of leukocytes and for their interactions with tumor cells, improving the adherence of the model to what is observed in laboratory experiments. Each system's solution realization is a family of biased random walk trajectories, affected by the chemotactic gradients and in turn affecting them. A sensitivity analysis with respect to the model parameters is performed in order to assess the effect of their variation on both tumor cells and on leukocyte dynamics. [ABSTRACT FROM AUTHOR]

Wound healing is a complex process to restore skin. Plant-derived bioactive compounds might be a source of substances for the treatment of wounds stalled in a non-resolving stage of wound healing. Oleanolic acid (OA), a pentacyclic triterpene, has shown favorable wound healing properties both in vitro and in vivo. Unfortunately, OA cannot be solubilized in aqueous media, and it needs to be helped by the use of dimethyl sulfoxide (DMSO). In this paper, we have shown that cyclodextrins (CDs) are a good alternative to DMSO as agents to deliver OA to cells, providing better features than DMSO. Cyclodextrins are natural macromolecules that show a unique tridimensional structure that can encapsulate a wide variety of hydrophobic compounds. We have studied the cyclodextrin-encapsulated form of OA with OA/DMSO, comparing their stability, biological properties for cell migration, and cell viability. In addition, detailed parameters related to cell migration and cytoskeletal reorganization have been measured and compared. Our results show that OA-encapsulateds compound exhibit several advantages when compared to non-encapsulated OA in terms of chemical stability, migration enhancement, and preservation of cell viability. [ABSTRACT FROM AUTHOR]

The high-squint airborne Synthetic Aperture Radar (SAR) has the ability to detect the target area flexibly, and the detection swath is significantly increased compared with the side-looking SAR system. Therefore, it is of great significance to carry out research on high-precision imaging methods for high-squint airborne SAR. However, the high-squint SAR echoes have large Range Cell Migration (RCM), resulting in severe range–azimuth coupling and strong spatial variation. In this paper, a Modified Range Doppler Algorithm (MRDA) is proposed to cope with these effects introduced by the significant RCM in high-squint airborne SAR imaging. The bulk compensation preprocessing is first adopted to remove the considerable RCM and severe cross-coupling in a two-dimensional frequency domain. Then, Non-Linear Chirp Scaling (NLCS) in the range direction is utilized to equalize the range-variant chirp rate caused by the residual RCM and coupling and, therefore, the consistent range phase compensation can be fulfilled in range frequency domain. The modified correlation processing is executed to compensate the residual Doppler phase modulation, the residual RCM and the range-variant cubic phase modulation, which guarantees the characteristics of high efficiency and high precision. The simulations have demonstrated that the MRDA can focus the SAR echoes with large squint angles more effectively than the algorithms based on the Linear Range Walk Correction (LRWC) method. [ABSTRACT FROM AUTHOR]

AbstractThe expression of both lactate dehydrogenase A (LDH-A) and glucose transporter type 1 (GLUT1) is high in pancreatic, thoracic and many other types of cancer. GLUT1 is also highly expressed in endothelial cells (EC), that play an important role in tumor metastasis. We investigated the effect of inhibition of LDH-A by NHI-2 and GLUT1 by PGL14 on cellular migration, a hallmark of metastasis, in relation to changes in intracellular purine nucleotide and nicotinamide adenine dinucleotide pools in a human microvascular endothelial cell line (HMEC-1). HMEC-1 were treated with NHI-2 and PGL14 alone or in combination. Cell migration was tested by the wound healing assay. The intracellular purine nucleotides and NAD+/NADH concentrations were measured using Reversed-Phase High Performance Liquid Chromatography (RP-HPLC). Both NHI-2 at 15 µM and 45 µM and PGL14 at 10 µM and 30 µM inhibited migration by 5 to 28% while the combination led to 46% inhibition. The drugs also decreased intracellular nucleotide pools, but only 45 µM NHI-2 altered energy charge and redox status in HMEC-1 cells. Inhibitors of glycolysis attenuated migration and the energy charge of EC and support further development of LDH-A and GLUT1 inhibitors to target cancer aggressiveness and metastasis. [ABSTRACT FROM AUTHOR]

The article features an interview with Mallika Bhattacharya, the first author of a paper titled "Steroid hormone signaling synchronizes cell migration machinery, adhesion and polarity to direct collective movement." The research focuses on the timing of cell migration and how steroid hormone signaling coordinates various mechanical aspects of cell movement. Bhattacharya discusses the challenges faced during the project, including scientific failures and the impact of the COVID-19 pandemic. She also highlights the significance of the Journal of Cell Science for publishing her paper and the support it provides to early-career researchers. Bhattacharya's contact details are provided for further inquiries. [Extracted from the article]

The echoes collected by wideband radar systems provide abundant information on target scatterers, which is beneficial to target detection, classification, and recognition. However, as the radar range resolution increases, range cell migration (RCM) during the coherent integration (CI) period happens much easier, which may cause a degradation of target detection probability. In addition, due to the target's orientation and structure relative to the radar, the distribution characteristics of the target scatterers in high-resolution range profiles (HRRPs) and the detection window length may vary from pulse to pulse, which may reduce the performance of traditional energy integration (EI) detectors. To solve those problems, moving range-spread target (RST) detection combining the modified keystone transform (MKT) and improved EI (IEI) is proposed in this paper. Firstly, based on waveform entropy minimization, MKT using hunter–prey optimization (HPO) is introduced to reduce the CI gain loss. The target Doppler ambiguity factor is estimated using such an effective optimization technique. Then, the IEI detector optimized by the adaptive threshold and detection window is utilized to achieve target detection, which minimizes the sensitivity of the traditional EI detector to the detection window length. The proposed method significantly improves the performance of moving RSTs in sea clutter without prior knowledge of the target Doppler ambiguity factor. Experiments are conducted by comparing the proposed method with other competing methods on both simulation data and real sea clutter data. The results demonstrate that the proposed method can obtain the CI more efficiently and has a higher detection probability. [ABSTRACT FROM AUTHOR]

Studying the effects of mechanical loads on living cells provides valuable information about their activity, vitality and intercellular communication. Mechanical stimuli have often a significant impact on cell migration, tissue remodeling and healing and other phenomena. This effects in micro scale affect also tissue structure, its mechanical characteristics and functionality. Special methods are needed to study deformation and biological responses of such small objects as cells. Moreover, in order to keep the cells alive during such tests, it is necessary to ensure appropriate environmental conditions. The methods of loading and examination cells can be categorized into several groups depending on the physical effects used in experiment. This paper provides a systematic review of the methods used in such studies and examples of mathematical modeling the mechanical response of cells to mechanical loads. Such models enable computational simulation of changes in cells and tissues excited by mechanical stress. [ABSTRACT FROM AUTHOR]

This document is a retraction notice from the journal Bioscience Reports. The article titled "MicroRNA-223 decreases cell proliferation, migration, invasion and enhances cell apoptosis in childhood acute lymphoblastic leukemia via targeting Forkhead box O1" is being retracted due to concerns raised about the data presented in the paper. The concerns include similarities with figures from other papers, inconsistencies in the data, and the authors' lack of response to the journal's queries. The Editorial Board has made the decision to retract the article. [Extracted from the article]

The article titled "Retraction: Downregulated microRNA-30b-3p inhibits proliferation, invasion and migration of glioma cells via inactivation of the AKT signaling pathway by upregulating RECK" has been retracted by Bioscience Reports. The retraction was prompted by concerns raised by a reader regarding the appearance of Western blots in the paper, which lacked background details and resembled blots from other papers. The Editorial Team also discovered undeclared image replacements in Figures 2B, 4A, and 5B. The authors have not responded to the concerns or queries from the journal. The decision to retract the article was made by the Editorial Board. [Extracted from the article]

With the rapid development and application of deep learning medical image recognition, natural language processing, and other fields, at the same time, deep learning has become the most popular research direction in the field of image processing and recognition. Through deep learning medical image recognition technology, it is of great significance to explore the research of miR-1301. The purpose of this article is to use an improved CNN neural network model algorithm combined to contrast the experimental groups and use deep learning medical imaging technology to study the mechanism by which miR-1301 inhibits the proliferation of carcinoma YD-38 cells through the PI3K/AKT pathway. This paper studies the method of image recognition of squamous cell carcinoma YD-38 cells using a convolutional neural network (CNN). First, a CNN classification model for the characteristics of YD-38 cell images is constructed. Then, pretraining and dropout technology are used to improve and optimize the proposed CNN model to improve the robustness of the model. In this paper, the miR mimic group and the miR blank group and the PI3K/AKT pathway inhibitor Wortmannin were selected to jointly treat YD-38 cells. The expression of mRNA in miR-1301 in HGF-1 was determined using RT-PCR (real and real-time fluorescence and YD-38 cells). The blank plasmids and the miR-1301 mimic (miR-1301 mimic) were transfected into YD-38 cells. The experiments were divided into two groups in the miR-1301 blank group and the miR-1301 simulation groups, respectively. The proliferation capacity of YD-38 cells was prepared in 1.5 ml sterile EP tubes and then diluted with medium for the proliferation of the cells. The scratch test and Transwell test were used to detect the effect of miR-1-3p on the migration and invasion of liver cancer cells. In this paper, CCK-8 experiment, clone formation experiment, flow cytometry, scratch experiment, and Transwell chamber experiment are used to analyze the effects of target gene CAAP1 on the proliferation, apoptosis, migration, and invasion of liver cancer cells. This paper uses CCK-8 to detect five kinds of the effect of miRNA on the proliferation ability of liver cancer cells and the effect of miR-1-3p on the proliferation ability of liver cancer cells. Experimental studies have shown that, compared with the miR blank group, the expression of PI3K and p-AKT was significantly downregulated in the miR mimic group after 24, 48, and 72 hours and the phosphorylation level of AKT was also significantly reduced P < 0.05 . [ABSTRACT FROM AUTHOR]

Tumor invasion follows a complex mechanism which involves cell migration and proliferation. To study the processes in which primary and secondary metastases invade and damage the normal cells, mathematical models are often extremely useful. In this paper, we present a mathematical model of acid-mediated tumor growth consisting of radially symmetric reaction–diffusion equations. The assumption on the radial symmetry of the solutions is imposed here in view that tumors present spherical symmetry at the microscopic level. Moreover, we consider various empirical mechanisms which describe the propagation of tumors by considering cancer cells, normal cells, and the concentration of H + ions. Among other assumptions, we suppose that these components follow logistic-type growth rates. Evidently, this is an important difference with respect to various other mathematical models for tumor growth available in the literature. Moreover, we also add competition terms of normal and tumor cells growth. We carry out a balancing study of the equations of the model, and a numerical model is proposed to produce simulations. Various practical remarks derived from our assumptions are provided in the discussion of our simulations. [ABSTRACT FROM AUTHOR]

Simple Summary: Although progress has been made in the treatment and survival of patients with a range of malignancies, the prognosis for patients harboring metastatic osteosarcoma (bone cancer) remains dismal due to the limited therapeutic options available. Endothelial progenitor cells (EPCs) mediate the angiogenic (blood vessel formation) switch in several cancers. Spatial proximity between EPCs and osteosarcoma in the bone led to the hypothesis that EPCs-osteosarcoma interactions may possibly promote osteosarcoma (OS) progression and aggressiveness. In the current paper, we demonstrate the non-physical role that EPCs play in OS migration and invasion, along with deciphering a potential underlying molecular mechanism. Our findings may pave the way toward the development of new EPCs-targeted therapies to inhibit OS metastasis and hence enhance the therapeutic efficacy of this devastating bone cancer. Background: Osteosarcoma (OS) mortality is attributed to lung metastases. Endothelial progenitor cells (EPCs) mediate the angiogenic switch in several cancers. The spatial proximity between EPCs and OS in the bone led to the hypothesis that EPCs-osteosarcoma interactions may possibly promote OS progression and aggressiveness. Methods: A PI3K inhibitor, Bevacizumab (an anti-VEGF-A antibody), and an anti-FGF2 antibody were added to the EPCs' conditioned medium (EPC-CM), and their impacts on OS cell (U2-OS and 143B) proliferation, migration, invasion, MMP9 expression, and AKT phosphorylation were determined. The autocrine role of VEGF-A was assessed using Bevacizumab treatment and VEGF-A silencing in OS cells. Toward this end, an orthotopic mouse OS model was established. Mouse and human tumors were immunolabeled with antibodies to the abovementioned factors. Results: EPC-CM enhanced osteosarcoma MMP9 expression, invasiveness, and migration via the PI3K/AKT pathway. The addition of Bevacizumab and an anti-FGF2 antibody to the EPC-CM diminished OS cell migration. The autocrine role of VEGF-A was assessed using Bevacizumab and VEGF-A silencing in OS cells, resulting in decreased AKT phosphorylation and, consequently, diminished invasiveness and migration. Consistently, OS xenografts in mice displayed high VEGF-A and FGF2 levels. Remarkably, lung metastasis specimens derived from OS patients exhibited marked immunolabeling of CD31, VEGF-A, and FGF2. Conclusions: EPCs promote OS progression not only by physically incorporating into blood vessels, but also by secreting cytokines, which act via paracrine signaling. EPCs induced in vitro MMP9 overexpression, invasion, and migration. Additional animal studies are warranted to further expand these results. These findings may pave the way toward the development of novel EPCs-targeted therapeutics aimed at blocking OS metastasis. [ABSTRACT FROM AUTHOR]

The coupling and spatial variation of range and azimuth parameters is the biggest challenge for bistatic forward-looking SAR (BFSAR) imaging. In contrast with the monostatic SAR and translational invariant bistatic SAR (TI-BSAR), the range cell migration (RCM), and Doppler parameters of high-speed bistatic forward-looking SAR (HS-BFSAR) have two-dimensional spatial variation characteristics, which makes it difficult to obtain SAR images with satisfactory global focusing. Firstly, based on the configuration of the spaceborne illuminator and high-speed forward-looking receiving platform, the accurate range-Doppler domain expression of the echo signal is derived in this paper. Secondly, using this analytical expression, a range nonlinear chirp scaling (NLCS) is proposed to equalize the RCM and equivalent range frequency modulation (FM) rate so that they can be uniformly processed in the two-dimensional frequency domain. Next, in the azimuth processing, the proposed method decomposes the Doppler contribution of the transmitter and receiver, respectively. Then, an azimuth NLCS is used to eliminate the spatial variation of the azimuth FM rate. Finally, a range-dependent azimuth filter is constructed to achieve azimuth compression. Simulation results validate the efficiency and effectiveness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a disease with complex pathogenesis, it is prone to metastasis, and its development involves abnormalities in multiple signaling pathways. Surgery, chemotherapy, radiotherapy, target therapy, and immunotherapy remain the main treatments for CRC, but improvement in the overall survival rate and quality of life is urgently needed. Traditional Chinese medicine (TCM) has a long history of preventing and treating CRC. It could affect CRC cell proliferation, apoptosis, cell cycle, migration, invasion, autophagy, epithelial–mesenchymal transition, angiogenesis, and chemoresistance by regulating multiple signaling pathways, such as PI3K/Akt, NF-κB, MAPK, Wnt/β-catenin, epidermal growth factor receptors, p53, TGF-β, mTOR, Hedgehog, and immunomodulatory signaling pathways. In this paper, the main signaling pathways and potential targets of TCM and its active ingredients in the treatment of CRC were systematically summarized, providing a theoretical basis for treating CRC with TCM and new ideas for further exploring the pathogenesis of CRC and developing new anti-CRC drugs. [ABSTRACT FROM AUTHOR]

Cancer cell migration, as the principal element of tumor invasion, involves different cellular mechanisms. Various modes of cell migration including single and collective motions contribute to the invasion patterns. The competition between adhesive cell–cell and cell–matrix forces is a key factor that determines such patterns. In this paper, we study a distinct shell-type mode of tumor invasion observed in brain and breast tumors. In this mode, cells at the outer layer of the tumor collectively move away from the core and form a shell-type shape. Both the core and the shell sustain a sharp interface between cells and the surrounding matrix. To model the preserved interface, we adopted a Cahn–Hilliard-type free energy relation with the contribution of the interfacial stress. This nonconvex form of free energy allows for cells to remain together and preserve the tumor core via adhesive cell–cell forces while separating the core from the surrounding matrix across a continuous sharp interface. In addition, the motion of the shell was modeled using the chemotactic migration of cells in response to the gradient of nutrients. The associated fluxes of cells were implemented in a general form of balance law. A non-Michaelis–Menten kinetics model was adopted for the proliferation rate of cells. The flux of nutrients was also modeled using a simple diffusion equation. The comparison between the model predictions and experimental observations indicates the ability of the model to manifest the salient features of the invasion pattern. [ABSTRACT FROM AUTHOR]

Experimental results on the immune response to cancer indicate that activation of cytotoxic T lymphocytes (CTLs) through interactions with dendritic cells (DCs) can trigger a change in CTL migration patterns. In particular, while CTLs in the pre-activation state move in a non-local search pattern, the search pattern of activated CTLs is more localised. In this paper, we develop a kinetic model for such a switch in CTL migration modes. The model is formulated as a coupled system of balance equations for the one-particle distribution functions of CTLs in the pre-activation state, activated CTLs and DCs. CTL activation is modelled via binary interactions between CTLs in the pre-activation state and DCs. Moreover, cell motion is represented as a velocity-jump process, with the running time of CTLs in the pre-activation state following a long-tailed distribution, which is consistent with a Lévy walk, and the running time of activated CTLs following a Poisson distribution, which corresponds to Brownian motion. We formally show that the macroscopic limit of the model comprises a coupled system of balance equations for the cell densities, whereby activated CTL movement is described via a classical diffusion term, whilst a fractional diffusion term describes the movement of CTLs in the pre-activation state. The modelling approach presented here and its possible generalisations are expected to find applications in the study of the immune response to cancer and in other biological contexts in which switch from non-local to localised migration patterns occurs. [ABSTRACT FROM AUTHOR]

This document is an interview with Artem Fokin, the first author of a paper titled "Inactivating negative regulators of cortical branched actin enhances persistence of single cell migration" published in the Journal of Cell Science. Fokin conducted the research while working as a postdoc in Alexis Gautreau's lab at Ecole Polytechnique in France. The paper explores the role of cortical branched actin in cell migration and the effects of inhibiting its antagonists. The research found that depleting these inhibitors resulted in increased cell migration, and combining three knockouts produced a significant gain in migration. The study also identified a checkpoint downstream of cortical branched actin that regulates an epithelial cell state and the role of vimentin in regulating migration persistence. Fokin chose the Journal of Cell Science for publication because it aligns with the focus of the research. [Extracted from the article]

Functional blood vessels are crucial to wound healing, and faster vascularization means faster tissue repair to some extent. Increasing numbers of pro-vascularization wound coverings are being developed and studied. Moreover, mechanical properties of the extracellular matrix can guide the behaviour of related cells to some degree. Studies have shown that the mechanical range of 1–7 kPa contributes to the differentiation of stem cells into endothelial cells and thus to the process of wound vascularization. Unfortunately, the regulatory mechanics of vascularizing wound coverings have been poorly studied. Silk fibroin (SF) has attracted much attention because of its good biocompatibility, degradability and adjustable mechanical properties. In this paper, silk scaffolds with mechanical properties of 2 kPa and 5.9 kPa were prepared by adjusting the mechanics of silk scaffolds in terms of freezing temperature and aligned structure. The mechanical properties of the 5.9 kPa aligned silk scaffold (ASS) showed good vascularization ability. By adjusting the intermediate conformation and physical structure of Silk fibroin (SF), the mechanical strength of the silk scaffold could be increased, enabling us to better understand the mechanical regulation mode. At the same time, the aligned structure of the aligned silk scaffold (ASS) promoted the migration and proliferation of cells related to wound repair to a certain extent. By adjusting the mechanical properties and physical structure of the material, an aligned silk scaffold with vascularization function was constructed, providing more possibilities for faster wound repair. • In this paper, silk scaffolds with mechanical properties of 2 kPa and 5.9 kPa were prepared by adjusting the mechanics of silk scaffolds in terms of freezing temperature and aligned structure. • By adjusting the intermediate conformation and physical structure of Silk fibroin (SF), the mechanical strength of the silk scaffold could be increased. • By adjusting the mechanical properties and physical structure of the material, an aligned silk scaffold with vascularization function was constructed, providing more possibilities for faster wound repair. [ABSTRACT FROM AUTHOR]

Cell migration is a pivotal biological process, whose dysregulation is found in many diseases including inflammation and cancer. Advances in microscopy technologies allow now to study cell migration in vitro, within engineered microenvironments that resemble in vivo conditions. However, to capture an entire 3D migration chamber for extended periods of time and with high temporal resolution, images are generally acquired with low resolution, which poses a challenge for data analysis. Indeed, cell detection and tracking are hampered due to the large pixel size (i.e., cell diameter down to 2 pixels), the possible low signal-to-noise ratio, and distortions in the cell shape due to changes in the z-axis position. Although fluorescent staining can be used to facilitate cell detection, it may alter cell behavior and it may suffer from fluorescence loss over time (photobleaching). Here we describe a protocol that employs an established deep learning method (U-NET), to specifically convert transmitted light (TL) signal from unlabeled cells imaged with low resolution to a fluorescent-like signal (class 1 probability). We demonstrate its application to study cancer cell migration, obtaining a significant improvement in tracking accuracy, while not suffering from photobleaching. This is reflected in the possibility of tracking cells for three-fold longer periods of time. To facilitate the application of the protocol we provide WID-U, an open-source plugin for FIJI and Imaris imaging software, the training dataset used in this paper, and the code to train the network for custom experimental settings. [ABSTRACT FROM AUTHOR]

In both physiological processes and disease contexts, migrating cells have the ability to adapt to conditions in their environment. As an in vivo model for this process, we use zebrafish primordial germ cells that migrate throughout the developing embryo. When migrating within an ectodermal environment, the germ cells form fewer and smaller blebs when compared with their behavior within mesodermal environment. We find that cortical tension of neighboring cells is a parameter that affects blebbing frequency. Interestingly, the change in blebbing activity is accompanied by the formation of more actin-rich protrusions. These alterations in cell behavior that correlate with changes in RhoA activity could allow the cells to maintain dynamic motility parameters, such as migration speed and track straightness, in different settings. In addition, we find that the polarity of the cells can be affected by stiff structures positioned in their migration path. This article has an associated 'The people behind the papers' interview. [ABSTRACT FROM AUTHOR]

Hilar cholangiocarcinoma (HCCA) is a highly aggressive biliary tract tumor. microRNAs (miRs) exert dual actions in various cancers. This paper seeks to expound on the functional mechanisms of miR-25-3p/dual specificity phosphatase 5 (DUSP5) in HCCA cell proliferation and migration. HCCA-related data were downloaded from GEO database to screen out differentially-expressed genes. The potential target miR (miR-25-3p) and its expression in HCCA were analyzed on Starbase. The binding relation between miR-25-3p and DUSP5 was confirmed by dual-luciferase assay. Levels of miR-25-3p and DUSP5 in FRH-0201 cells and HIBEpics were determined by RT-qPCR and Western blot. miR-25-3p and DUSP5 levels were intervened with to explore their effects on FRH-0201 cells. The apoptosis, proliferation, migration, and invasion of FRH-0201 cells were evaluated by TUNEL, CCK8, scratch healing, and Transwell assays. Flow cytometry was conducted to assess FRH-0201 cell cycle. Levels of cell cycle-related proteins were determined by Western blot. DUSP5 was weakly-expressed and miR-25-3p was highly-expressed in HCCA samples and cells. miR-25-3p targeted DUSP5. miR-25-3p suppressed FRH-0201 cell apoptosis and increased cell proliferation, migration, and invasion. DUSP5 overexpression partially abrogated miR-25-3p overexpression-exerted effects on FRH-0201 cells. miR-25-3p stimulated G1/S phase transition of FRH-0201 cells by targeting DUSP5. miR-25-3p regulated HCCA cell cycle and facilitated cell proliferation and migration by targeting DUSP5. [ABSTRACT FROM AUTHOR]

Platelet‐rich plasma (PRP) has become an accepted and general wound healing approach with an extremely wide range of applications. Despite considerable diversity in the composition of platelet‐rich plasma products that are applied in specific wound healing usage, it is widely recognised that such diverse platelet‐rich plasma complex mixtures routinely display hormetic‐like biphasic concentrations that are independent of the tissue treated and endpoints measured. The present paper is the first to place the area of platelet‐rich plasma‐biomedical research and applications within an hormetic framework. The platelet‐rich plasma area is also unique as it represents the application of the hormetic concept to the issue of complex biological mixtures. [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]