Cell Movement Research Articles

CHUP1 restricts chloroplast movement and effector-triggered immunity in epidermal cells.

Chloroplast Unusual Positioning 1 (CHUP1) plays an important role in the chloroplast avoidance and accumulation responses in mesophyll cells. In epidermal cells, prior research showed silencing CHUP1-induced chloroplast stromules and amplified effector-triggered immunity (ETI); however, the underlying mechanisms remain largely unknown. CHUP1 has a dual function in anchoring chloroplasts and recruiting chloroplast-associated actin (cp-actin) filaments for blue light-induced movement. To determine which function is critical for ETI, we developed an approach to quantify chloroplast anchoring and movement in epidermal cells. Our data show that silencing NbCHUP1 in Nicotiana benthamiana plants increased epidermal chloroplast de-anchoring and basal movement but did not fully disrupt blue light-induced chloroplast movement. Silencing NbCHUP1 auto-activated epidermal chloroplast defense (ECD) responses including stromule formation, perinuclear chloroplast clustering, the epidermal chloroplast response (ECR), and the chloroplast reactive oxygen species (ROS), hydrogen peroxide (H2O2). These findings show chloroplast anchoring restricts a multifaceted ECD response. Our results also show that the accumulated chloroplastic H2O2 in NbCHUP1-silenced plants was not required for the increased basal epidermal chloroplast movement but was essential for increased stromules and enhanced ETI. This finding indicates that chloroplast de-anchoring and H2O2 play separate but essential roles during ETI.

The hGIDGID4 E3 ubiquitin ligase complex targets ARHGAP11A to regulate cell migration.

The human CTLH/GID (hGID) complex emerged as an important E3 ligase regulating multiple cellular processes, including cell cycle progression and metabolism. However, the range of biological functions controlled by hGID remains unexplored. Here, we used proximity-dependent biotinylation (BioID2) to identify proteins interacting with the hGID complex, among them, substrate candidates that bind GID4 in a pocket-dependent manner. Biochemical and cellular assays revealed that the hGIDGID4 E3 ligase binds and ubiquitinates ARHGAP11A, thereby targeting this RhoGAP for proteasomal degradation. Indeed, GID4 depletion or impeding the GID4 substrate binding pocket with the PFI-7 inhibitor stabilizes ARHGAP11A protein amounts, although it carries no functional N-terminal degron. Interestingly, GID4 inactivation impairs cell motility and directed cell movement by increasing ARHGAP11A levels at the cell periphery, where it inactivates RhoA. Together, we identified a wide range of hGIDGID4 E3 ligase substrates and uncovered a unique function of the hGIDGID4 E3 ligase regulating cell migration by targeting ARHGAP11A.

Abstract A031: ECM architecture drives distinct evolutionary patterns of tumor immune escape and elimination in breast cancer

Abstract Cancer progression poses a clinical hurdle due to tumor heterogeneity that contributes to treatment resistance and immune evasion. While the adaptive immune system can effectively eliminate cancer in certain instances, tumor escape remains challenging. The immune microenvironment plays an important role in this process. One unanswered question is the role of ECM geometry, also known as Tumor Associated Collagen Signatures (TACS), and its effects on tumor immune recognition. In solid malignancies, ECM geometry has been associated with disease stage and T cell infiltration. Specifically, empirically observed ECM topologies are frequently categorized based on fiber arrangement: random fibers (TACS1), circumferentially aligned fibers (TACS2), and radially arranged fibers (TACS3). Even though a clear negative correlation between TACS and patient survival has been established, the specific roles and extent of TACS in T cell-driven cancer evolution remain uncharacterized. The precise mechanisms underlying how TACS influences cell movement are still not fully elucidated, with divergent opinions on whether and how the ECM mediates immune cell infiltration. At present, we currently lack a physical model relating the impact of TACS on the spatial co-evolution between an adaptive immune repertoire and a heterogeneous population of evading cancer cells. Here, we developed the EVO-ACT (EVOlutionary Agent-based Cancer T cell interaction) model, which is based on the Gillespie algorithm, to study the effects of TACS on tumor evolution and dynamical tumor-T cell interactions. Our analysis of tumor-T cell interactions across three TACS types reveals distinct migration patterns, with TACS3 showing the highest efficiency, TACS1 intermediate, and TACS2 the lowest. TACS impacts T cells more than tumors, with stronger chemokine gradients aiding T cell infiltration. Our model suggests that despite TACS2's limited efficiency, it cannot fully impede T cell infiltration. Varied migration efficiencies lead to diverse T cell infiltration patterns and immunoediting levels. TACS3 shows a benefit to immune recognition and higher survival, contrary to lower survival in TACS3 patients observed clinically in breast cancer. Our results indicate that only after introducing phenotypic changes, such as Epithelial-Mesenchymal Transition (EMT), and noting that EMT occurs exclusively after the TACS2-TACS3 progression, can our findings successfully explain the clinically observed trends. Considering mesenchymal tumor cells' ability to upregulate PD-1/PD-L1, we explore TACS-specific tumor evolution's impact on PD-1/PD-L1 inhibitor responses and patient survival. We observe higher tumor escape rates and lower survival in TACS3 compared to TACS2. Thus, TACS3 alone does not account for lower survival in breast cancer; TACS3-associated late-stage cancer byproducts like EMT and elevated checkpoint expression significantly decrease survival. Citation Format: Yijia Fan, Jason Tomas George. ECM architecture drives distinct evolutionary patterns of tumor immune escape and elimination in breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A031.

Filtered partial differential equations: a robust surrogate constraint in physics-informed deep learning framework

Embedding physical knowledge into neural network (NN) training has been a hot topic. However, when facing the complex real world, most of the existing methods still strongly rely on the quantity and quality of observation data. Furthermore, the NNs often struggle to converge when the solution to the real equation is very complex. Inspired by large eddy simulation in computational fluid dynamics, we propose an improved method based on filtering. We analysed the causes of the difficulties in physics-informed machine learning, and proposed a surrogate constraint (filtered partial differential equation, FPDE) of the original physical equations to reduce the influence of noisy and sparse observation data. In the noise and sparsity experiment, the proposed FPDE models (which are optimized by FPDE constraints) have better robustness than the conventional PDE models. Experiments demonstrate that the FPDE model can obtain the same quality solution with 100 % higher noise and 12 % quantity of observation data of the baseline. Besides, two groups of real measurement data are used to show the FPDE improvements in real cases. The final results show that the FPDE still gives more physically reasonable solutions when facing the incomplete equation problem and the extremely sparse and high-noise conditions. The proposed FPDE constraint is helpful for merging real-world experimental data into physics-informed training, and it works effectively in two real-world experiments: simulating cell movement in scratches and blood velocity in vessels.

Peripheral straightness leads to shape diversification during formations of entire leaves.

The ways to read out positional information are essential to determine final shapes in developmental processes. Relative shaping to different sizes of positional information enables robust morphogenesis; however, the same difference sometimes causes diversity. Different responses to a positional information will enable such switching of identical/diverse shapes, though detail mechanisms remain unknown. In this paper, we describe growing forms by constructing the contour of a two-dimensional object using propagating points and segments connecting them. In plant morphogenesis that lacks almost cell movements, tissue growth accompanied by cell divisions is central. We focused on peripheral cell composition in leaf formation as a frame. The growth with or without cell division on the periphery was analyzed with simple algorithms. We calculated the shapes of entire leaves with different ovality using combined growth algorithms as a model. Responces of the respective algorithms to simple positional information were explored to seek the origin of the shape diversification. The algorithm for "growth with cell divisions" maintained identical shapes; however, diverse shapes were generated by the algorithm "growth without cell division" with gradients. The simplified model allowed us to interpret the oval shape diversity due to slants on edges. We concluded that peripheral straightness can generate shape diversity, at least in leaf morphogenesis.

Abstract A005: Microbind affinity blood filter platform technology with affinity for heparan sulfate rapidly removes circulating epithelial tumor and cancer stem cells while downregulating VEGF A in patients with advanced and refractory solid tumors

Abstract Background: Vascular endothelial-derived growth factor A(VEGFA) has been proven to be integral in the molecular pathogenesis of metastasis and tumor growth. It is known that VEGF is responsible for encoding a heparin-binding protein, which exists as a disulfide-linked homodimer which serves to promote the propagation and movement of vascular endothelial cells. This is essential for both pathological and physiological angiogenesis. CETC and cancer stem cells are potent secretors of VEGFA which is an essential cytokine that facilitates new vascular vessel formation, thus further enabling metastatic tumor growth. Methods: We developed a new extracorporeal microbind affinity blood filter platform technology with active heparane sulfate receptors (onco seraph). Heparin is cleaved into short chains which are permanently covalently bound to ultrahigh molecular weight polyethylene (UHMWPE) surfaces to create a new composition of matter. Liquid biopsy established high capacity for the rapid removal of CETC and PDAC cancer stem cells. Onco seraph was investigated in a dose escalation phase I/II clinical trial in adult patients with advanced and relapsed/refractory solid (what) and/or PDAC after standard of care and other lines of therapy failed in preventing disease progression. Results: To date 12 patients have been treated with onco seraph. No patient experienced treatment related adverse effects. Best responses include complete responses and stable disease at a low oncoseraph dose. Greatest efficacy was observed for patients whose liquid biopsy revealed significant and rapid reduction of CETC and cancer stem cells, followed by greater than 50% reduction in circulating VEGFA. Conclusions: This data supports the conclusion that the onco seraph platform technology is safe and has a high therapeutic value as an extracorporeal treatment for metastatic solid tumors refractory to standard of care. Citation Format: Sanja ILIC, Vedran Premuzic, Robert Ward. Microbind affinity blood filter platform technology with affinity for heparan sulfate rapidly removes circulating epithelial tumor and cancer stem cells while downregulating VEGF A in patients with advanced and refractory solid tumors [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A005.

DDDR-16. SORTING TO ENRICH FOR CHEMOTHERAPEUTIC-RESISTANT GLIOMA CELLS BASED ON UNIQUE MEMBRANE PROPERTIES

Abstract Glioblastoma, astrocytoma, and oligodendroglioma comprise a class of aggressive and deadly brain tumors called diffuse gliomas. Around 20,000 glioma cases are diagnosed yearly in the US alone. The current standard chemotherapy treatment, temozolomide (TMZ), is insufficient as the 5-year survival rate of glioblastoma patients is as low as 8%. This is due to the presence of TMZ-resistant cells within tumors that lead to chemoresistance and tumor recurrence. Thus, studying the molecular properties of TMZ-resistant cells would enable more effective means of targeting them and thus improve patient outcomes. We leveraged dielectrophoresis (DEP), a phenomenon by which non-uniform electric fields induce differential movement of cells, as a novel label-free technique to sort glioma cells based on their membrane electrophysiological properties. We were able to successfully use DEP to sort cells from glioblastoma and oligodendroglioma established cell lines, which yielded fractions that differed in membrane capacitance, the membrane’s ability to store charge. Interestingly, the DEP-sorted cell fractions also exhibited significant differences in TMZ resistance, indicating that we were able to use DEP to enrich for TMZ-resistant cells. Further, the differences in TMZ resistance were coupled with their membrane capacitance differences. Because we previously found that changes in membrane capacitance were linked to differences in glycosylation, we utilized lectin analysis to assess glycan expression of DEP-sorted oligodendroglioma cells. Our data show that TMZ-resistant oligodendroglioma cells enriched from DEP sorting had reduced levels of mannose glycans compared to less TMZ-resistant fractions. Collectively, our novel findings demonstrate (a) TMZ-resistant glioma cells can be enriched by DEP, and (b) TMZ resistance is correlated with membrane capacitance and cell surface glycosylation. These findings could enable further characterization of TMZ-resistant cells to better understand molecular mechanisms of TMZ resistance and the development of more effective treatment strategies for gliomas through targeting membrane properties such as glycosylation.

Conditioned Extracellular Vesicles Derived from Dedifferentiated Fat Cells Promote Bone Regeneration by Altering MicroRNAs

Background: Extracellular vesicles (EVs) derived from stem cells demonstrate significant potential in bone regeneration. Adipose tissue is regarded as a stem cell reservoir with abundant reserves and easy accessibility. Compared to adipose-derived stem cells (ASCs), dedifferentiated fat cells (DFATs) possess similar stem cell characteristics but exhibit greater proliferative capacity, higher homogeneity, and an enhanced osteogenic differentiation potential. This study is the first to examine the effect of DFATs-derived EVs on bone regeneration and elucidate their potential mechanisms of action. Methods: Primary DFATs were cultured using the “ceiling culture” method and EVs were isolated by ultracentrifugation and characterized. Experiments were performed to assess the impact of the EVs on the proliferation, migration, and osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Subsequently, high-throughput miRNA sequencing was conducted on the EVs derived from DFATs that had undergone 0 days (0d-EVs) and 14 days (14d-EVs) of osteogenic differentiation. Results: The results indicated that the EVs derived from DFATs which experienced 14 days of osteogenic induction significantly promoted the proliferation, migration, and osteogenic differentiation of BMSCs. High-throughput sequencing results revealed that up-regulated miRNAs in the 14d-EVs were primarily involved in biological processes such as the Notch signaling pathway and the positive regulation of cell movement and migration. The target genes of these differently expressed miRNAs were enriched in osteogenesis-related signaling pathways. Conclusion: This study innovatively demonstrated that conditioned EVs (14d-EVs) derived from DFATs promoted the osteogenic differentiation of BMSCs via miRNAs, offering a promising cell-free therapeutic option for bone defect.

Visualization of giant Mimivirus in a movie for biology classrooms.

We have developed a new observation chamber for Mimivirus-infected Acanthamoeba to create dynamic visual teaching materials for virus education suitable for high school and university biology courses. We conducted experiments and captured a movie showcasing the infection process of Acanthamoeba cells by mimiviruses. In this educational film, we successfully recorded the active movement of healthy Acanthamoeba cells across the surface of a culture flask under an agarose gel. After Mimivirus infection, the movement of the Acanthamoeba cells gradually slowed and eventually stopped. This cessation coincided with the development of the Mimivirus virion factory, which began producing new virions on the surface of the host cells. Moreover, we captured continuous footage of a single cell throughout the viral proliferation process, thereby illustrating the viral proliferation in real time. This educational movie, which visually demonstrates the proliferation of Mimivirus within host cells, acts as an effective teaching tool. Moreover, it enhances students' understanding of virus proliferation mechanisms and highlights the biological significance of viruses, their impact on host cell fate, and their role in ecosystems.

Integrin α2 in the microenvironment and the tumor compartment of digestive (gastrointestinal) cancers: emerging regulators and therapeutic opportunities

Integrins are a family of cell surface membrane receptors and play a crucial role in facilitating bidirectional cell signaling. Integrin α2 (ITGA2) is expressed across a range of cell types, including epithelial cells, platelets, megakaryocytes, and fibroblasts, where it functions as a surface marker and it is implicated in the cell movements. The most recent findings have indicated that ITAG2 has the potential to function as a novel regulatory factor in cancer, responsible for driving tumorigenesis, inducing chemoresistance, regulating genomic instability and remodeling tumor microenvironment. Hence, we primarily focus on elucidating the biological function and mechanism of ITGA2 within the digestive tumor microenvironment, while highlighting its prospective utilization as a therapeutic target for cancer therapy.

Cyclic stretch regulates epithelial cell migration in a frequency dependent manner via intercellular vinculin recruitment

The epithelial microenvironment is incredibly dynamic, subjected to mechanical cues including cyclic stretch. While cyclic cell stretching platforms have revealed epithelial cell reorientation and gap formation, few studies have investigated the long-term effects of cyclic stretch on cell migration. We measured the migratory response of the epithelium to a range of physiologically relevant frequencies and stretch. Our results indicate that lower stretch frequencies (i.e., 0.1 Hz) suppress epithelial migration, accompanied by cell reorientation and high cell shape solidity. We found that this response is also accompanied by increased recruitment of vinculin to cell-cell contacts, and this recruitment is necessary to suppress cell movements. These results confirm the mechanosensitive nature of vinculin within the adherens junction, but independently reveal a novel mechanism of low frequency stress response in supporting epithelial integrity by suppressing cell migration.

Talin-1 variants associated with spontaneous coronary artery dissection (SCAD) highlight how even subtle changes in multi-functional scaffold proteins can manifest in disease.

Variants of talin-1 (TLN1) have recently been linked with spontaneous coronary artery dissection (SCAD) a condition where a tear can form in the wall of a heart artery necessitating immediate medical care. One talin-1 variant, A2013T, has an extensive familial pedigree of SCAD, which led to the screening for, and identification of, further talin-1 variants in SCAD patients. Here we evaluated these variants with commonly used pathogenicity prediction tools and found it challenging to reliably classify SCAD-associated variants, even A2013T where the evidence of a causal role is strong. Using biochemical and cell biological methods, we show that SCAD-associated variants in talin-1, which would typically be classified as non-pathogenic, still cause a measurable impact on protein structure and cell behaviour, including cell movement and wound healing capacity. Together, this indicates that even subtle variants in central mechanosensitive adapter proteins, can give rise to significant health impacts at the individual level, suggesting the need for a possible re-evaluation of the scoring criteria for pathogenicity prediction for talin variants.

Hybrid discrete‐continuum modeling of tumor‐immune interactions: Fractional time and space analysis with immunotherapy

In this paper, we introduce an innovative hybrid discrete‐continuum model that provides a comprehensive framework for understanding the intricate interactions between tumor cells, immune cells, and the effects of immunotherapy. This study distinguishes itself by addressing the limitations of traditional diffusion models, which often fail to capture the irregular and nonlocal movements of cells within the complex tumor microenvironment. To overcome these challenges, we employ fractional time derivatives and the fractional Laplacian operator, offering a more accurate representation of anomalous diffusion processes that are critical in cancer dynamics. Our research begins with a rigorous mathematical analysis, where we establish the global existence of a unique mild solution, laying a solid theoretical foundation for the model. A key innovation of our study is the introduction of the “invasion threshold,” a critical parameter inspired by the next‐generation operator used in epidemiological modeling. This threshold provides a powerful tool for determining the existence and stability of equilibrium points, offering deep insights into the conditions that either promote or inhibit tumor growth under immunotherapeutic interventions. By integrating a hybrid discrete‐continuum approach, we capture the individual behavior of each cell, allowing for a more detailed exploration of the dynamic interplay within the tumor microenvironment. This model not only advances our understanding of tumor‐immune interactions but also holds potential for informing more effective therapeutic strategies, making a significant contribution to the field of mathematical oncology.

Emerging roles of auxin in plant abiotic stress tolerance.

Plants are continuously attacked by several biotic and abiotic factors. Among abiotic factors, heat, cold, drought, and salinity are common stresses. Plants produce several hormones as their main weapon in fightback against these stresses. Among these hormones, the role of auxin is well established in regulating plant growth and development at various scales. However, in recent literature, the important role of auxin in abiotic stress tolerance has emerged. Several auxin signalling and transport mutants exhibit heat, drought, and salinity-related phenotypes. Among them, auxin-mediated hypocotyl elongation and root growth in response to increased heat are of importance due to the continuous rise in global temperature. Auxin is also involved in regulating and recruiting specialized metabolites like aliphatic glucosinolate to defend themselves from drought stress. Aliphatic glucosinolate (A-GLS) regulates guard cell closure using auxin, which is independent of the major abiotic stress hormone abscisic acid. This regulatory mechanism serves as an additional layer of guard cell movement to protect plants from drought. Transferring the aliphatic glucosinolate pathway into non-brassica plants such as rice and soybean holds the promise to improve drought tolerance. In addition to these, post-translational modification of auxin signalling components and redistribution of auxin efflux transporters are also playing important roles in drought and salt tolerance and, hence, may be exploited to breed drought-tolerant crops. Also, reactive oxygen species, along with peptide hormone and auxin signalling, are important in root growth under stress. In conclusion, we summarize recent discoveries that suggest auxin is involved in various abiotic stresses.

Suppression of Pcdh8/paraxial protocadherin is required for efficient neighbor exchange in morphogenetic cell movement during zebrafish notochord formation

In certain forms of collective cell migration, changes in neighboring cells (neighbor exchange, NE) are essential. In the axial mesoderm in zebrafish, for example, the notochord is established through cell movements known as convergence and extension (C&E), which involves NE. For NE to occur efficiently, the balance between cell-scale and supracellular stresses plays a crucial role, but the molecular basis of how these stresses are controlled remains unclear. In this study, we focused on Pcdh8/Paraxial protocadherin (PAPC), which is specifically suppressed in the region (notochord) where and at the time (early gastrula) when extensive C&E occurs. Forced expression of PAPCΔC (PAPC lacking its intracellular domain) persisted in the developing notochord and resulted in morphogenetic defects in zebrafish. PAPCΔC was found to downregulate NE in the notochord in a homophilic contact-dependent manner. By examining oil droplets inserted between cells, we revealed that while cell-scale stresses were apparently unaffected, the direction of bias in the supracellular stresses was stabilized by the introduction of PAPCΔC in the notochordal region. Taken together, our results suggest that suppression of PAPC in the notochord is required to modify supracellular stresses and provide the conditions in which NE occurs efficiently, thus promoting morphogenetic cell movements.

Early embryonic development of the German cockroach Blattella germanica

BackgroundEarly embryogenesis is characterized by dramatic cell proliferation and movement. In most insects, early embryogenesis includes a phase called the uniform blastoderm, during which cells evenly cover the entirety of the egg. However, the embryo of the German cockroach, Blattella germanica, like those of many insects within the super order Polyneoptera, does not have a uniform blastoderm; instead, its first cells condense rapidly at the site of a future germband. We investigated early development in this species in order to understand how early gene expression is or is not conserved in these insect embryos with distinct early cell behaviors.ResultsWe present a detailed time series of nuclear division and distribution from fertilization through germband formation and report patterns of expression for the early patterning genes hunchback, caudal, and twist in order to understand early polarization and mesoderm formation. We show a detailed time course of the spatial expression of two genes involved in the segmentation cascade, hedgehog and even-skipped, and demonstrate two distinct dynamics of the segmentation process.ConclusionsDespite dramatic differences in cell distribution between the blastoderms of many Polyneopteran insects and those of more well-studied developmental models, expression patterns of early patterning genes are mostly similar. Genes associated with axis determination in other insects are activated relatively late and are probably not maternally deposited. The two phases of segmentation—simultaneous and sequential—might indicate a broadly conserved mode of morphological differentiation. The developmental time course we present here should be of value for further investigation into the causes of this distinct blastoderm type.

Computational Identification of Migrating T cells in Spatial Transcriptomics Data.

T cells are the central players in antitumor immunity, and effective tumor killing depends on their ability to infiltrate into the tumor microenvironment (TME) while maintaining normal cytotoxicity. However, late-stage tumors develop immunosuppressive mechanisms that impede T cell movement and induce exhaustion. Investigating T cell migration in human tumors in vivo could provide novel insights into tumor immune escape, although it remains a challenging task. In this study, we developed ReMiTT, a computational method that leverages spatial transcriptomics data to track T cell migration patterns within tumor tissue. Applying ReMiTT to ovarian tumor samples, we identified key genes and pathways that enriched on algorithm-identified T cell migration trails, including leukocyte chemotaxis, cell-cell adhesion, and ECM remodeling. We also characterized the phenotypes of T cells on the migrating trails, suggesting that regulatory T cells may accompany cytotoxic T cells during migration. Our findings provide a novel approach to studying T cell migration and interactions within the TME, offering new insights into tumor-immune dynamics.

Immunology of Stress: A Review Article.

Stress significantly impacts the immune system, affecting susceptibility to illness and overall health. This review examines the intricate relationship between stress and the immune system, offering insights having practical implications for health and disease prevention. Stress can significantly trigger molecular and immune modulation, affecting the distribution and trafficking of immune cells in various organs and altering their composition in the blood. The review delves into two key pathways connecting stress and immunity: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Stress activates the neuroendocrine system and triggers microglia in the brain, releasing stress hormones and neurotransmitters that modulate the function and movement of immune cells. Acute stress can temporarily strengthen immunity and promote protection during infection; in contrast, chronic stress dysregulates or inhibits immune functions. Chronic stress causes an increase in cortisol levels through the HPA axis, ultimately suppressing the immune response. Recognizing stress triggers and implementing effective stress management techniques can significantly impact individuals' well-being. This review indicates that immune cells express genes differentially in response to stress, suggesting individual variabilities in the immune response against stress. This underscores the need for a personalized approach to stress management. This review also highlights the potential link between chronic stress and autoimmune disorders and warrants further investigation.

Global existence and boundedness in a two‐dimensional parabolic chemotaxis system with competing attraction and repulsion effects

In this paper, we investigate a chemotaxis system under homogeneous Neumann boundary conditions within a bounded domain with a smooth boundary. The system describes the movement of cells in response to two chemical signal substances: one acts as a chemoattractant, while the other serves as a chemorepellent, both produced by the cells. The system takes into account chemotactic sensitivity in the reaction movement when detecting these chemicals. Under certain assumptions, we demonstrate the existence of a unique global bounded classical solution for the proposed problem. To further understand the time evolution of the system's solutions, we conduct numerical experiments and analyze the dynamic properties of the norm of the solutions with respect to variations in chemical production rates.

Disturbing microtubule-endoplasmic reticulum dynamics by gold nanoclusters for improved triple-negative breast cancer treatment.

Microtubules are highly dynamic structures, and their dynamic instability is indispensable for not only cell growth and movement, but also stress responses, such as endoplasmic reticulum (ER) stress. Docetaxel, a microtubule targeting agent (MTA), is the first-line drug for cancer treatment by simultaneously promoting microtubule dysregulation- and ER stress-induced cell death. However, it also causes adverse effects and drug resistance, especially in triple-negative breast cancer (TNBC) with a poor prognosis and high mortality rate. In this study, we developed a peptide-templated gold nanocluster, namely GA. GA significantly sensitizes TNBC cells to docetaxel, causing severe cell death. This effect is further validated by a 3D tumor spheroid model. Mechanistically, GA disrupted microtubule dynamic instability, meanwhile promoting PERK-mediated ER stress. Interestingly, ER stress inhibitors profoundly suppressed microtubule dysregulation, suggesting a retrograde regulation of ER stress on microtubules. In vivo, the combined administration of docetaxel and GA significantly suppresses tumor growth while docetaxel alone cannot. GA similarly elevated the level of caspases and PERK within tumors as in vitro. Importantly, GA treatment also profoundly promoted the production of anti-tumor inflammatory cytokines. Collectively, we developed an ER-microtubule regulatory nanomaterial that enhanced the therapeutic effect of docetaxel by elevating tumor cell death and anti-tumor cytokine production, providing a potential supplemental strategy for TNBC treatment.