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Chemotactic bacteria not only navigate chemical gradients, but also shape their environments by consuming and secreting attractants. Investigating how these processes influence the dynamics of bacterial populations has been challenging because of a lack of experimental methods for measuring spatial profiles of chemoattractants in real time. Here, we use a fluorescent sensor for aspartate to directly measure bacterially generated chemoattractant gradients during collective migration. Our measurements show that the standard Patlak-Keller-Segel model for collective chemotactic bacterial migration breaks down at high cell densities. To address this, we propose modifications to the model that consider the impact of cell density on bacterial chemotaxis and attractant consumption. With these changes, the model explains our experimental data across all cell densities, offering insight into chemotactic dynamics. Our findings highlight the significance of considering cell density effects on bacterial behavior, and the potential for fluorescent metabolite sensors to shed light on the complex emergent dynamics of bacterial communities.

While the involvement of actin polymerization in cell migration is well-established, much less is known about the role of transmembrane water flow in cell motility. Here, we investigate the role of water influx in a prototypical migrating cell, the neutrophil, which undergoes rapid, directed movement to sites of injury, and infection. Chemoattractant exposure both increases cell volume and potentiates migration, but the causal link between these processes are not known. We combine single-cell volume measurements and a genome-wide CRISPR screen to identify the regulators of chemoattractant-induced neutrophil swelling, including NHE1, AE2, PI3K-gamma, and CA2. Through NHE1 inhibition in primary human neutrophils, we show that cell swelling is both necessary and sufficient for the potentiation of migration following chemoattractant stimulation. Our data demonstrate that chemoattractant-driven cell swelling complements cytoskeletal rearrangements to enhance migration speed.

Oxygen is an essential substance for the maintenance of human life. It is also widely used in clinical and diving medicine. Although oxygen is crucial for survival, too much oxygen can be harmful. Excessive oxygen inhalation in a short period of time can lead to injury, and the lung is one of the main target organs. Acute lung injury (ALI) induced by hyperbaric oxygen (HBO) is notably more severe than that caused by normobaric oxygen, yet systematic research on such injury and its regression is scarce. In this study, two independent experiments were designed. In the first experiment, mice were exposed to 2 atmospheres absolute (ATA), ≥95% oxygen for 2, 4, 6, and 8 h. Changes in lung histopathology, inflammation and expression of chemokines, alveolar-capillary barrier, and 8-OHdG were detected before and after the exposure. In the second experiment, these parameters were measured at 0 h, 12 h, and 24 h following 6 h of exposure to 2 ATA of ≥95% oxygen. Research indicates that ALI induced by HBO is characterized histologically by alveolar expansion, atelectasis, inflammatory cell infiltration, and hemorrhage. At 2 ATA, significant changes in the alveolar-capillary barrier were observed after more than 95% oxygen exposure for 4 h, as evidenced by increased Evans blue (EB) extravasation (p = 0.0200). After 6 h of HBO exposure, lung tissue pathology scores, 8-OHdG levels, and inflammatory and chemotactic factors (such as Il6, CCL2, CCL3, CXCL5, and CXCL10), intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1 (VCAM1) were significantly elevated. Compared to lung injury caused by normobaric oxygen, the onset time of injury was significantly shortened. Additionally, it was observed that these markers continued to increase after leaving the HBO environment, peaking at 12 h and starting to recover at 24 h, indicating that the peak of inflammatory lung injury occurs within 12 h post-exposure, with recovery beginning at 24 h. This contradicts the common belief that lung injury is alleviated upon removal from a high-oxygen environment. However, EB levels, which reflect damage to the alveolar-capillary barrier, and VE-Cadherin (VE-Cad), tight junction protein 1 (ZO-1), ICAM1, and VCAM1 remained significantly altered 24 h after leaving the HBO environment. This suggests that the alveolar-capillary barrier is the most sensitive and slowest recovering part of the lung injury induced by HBO. These findings can provide insights into the pathogenesis and progression of lung injury caused by HBO and offer references for identifying corresponding intervention targets. [ABSTRACT FROM AUTHOR]

Human neutrophils respond to multiple chemoattractants to guide their migration from the vasculature to sites of infection and injury, where they clear pathogens and amplify inflammation. To properly focus their responses during this complex navigation, neutrophils prioritize pathogen- and injury-derived signals over long-range inflammatory signals, such as the leukotriene LTB4, secreted by host cells. Different chemoattractants can also drive qualitatively different modes of migration even though their receptors couple to the same Gαi family of G proteins. Here, we used live-cell imaging to demonstrate that the responses differed in their signaling dynamics. Low-priority chemoattractants caused transient responses, whereas responses to high-priority chemoattractants were sustained. We observed this difference in both primary neutrophils and differentiated HL-60 cells, for downstream signaling mediated by Ca2+, a major regulator of secretion, and Cdc42, a primary regulator of polarity and cell steering. The rapid attenuation of Cdc42 activation in response to LTB4 depended on the phosphorylation sites Thr308 and Ser310 in the carboxyl-terminal tail of its receptor LTB4R in a manner independent of endocytosis. Mutation of these residues to alanine impaired chemoattractant prioritization, although it did not affect chemoattractant-dependent differences in migration persistence. Our results indicate that distinct temporal regulation of shared signaling pathways distinguishes between receptors and contributes to chemoattractant prioritization.

SDF-1/CXCL12 is a unique chemotactic factor with multiple functions on various types of precursor cells, all carrying the cognate receptor CXCR4. Whereas individual biological functions of SDF-1/CXCL12 have been well documented, practical applications in medicine are insufficiently studied. This is explained by the complex multifunctional biology of SDF-1 with systemic and local effects, critical dependence of SDF-1 activity on aminoterminal proteolytic processing and limited knowledge of applicable modulators of its activity. We here present new insights into modulation of SDF-1 activity in vitro and in vivo by a macromolecular compound, chlorite-oxidized oxyamylose (COAM). COAM prevented the proteolytic inactivation of SDF-1 by two inflammationassociated proteases: matrix met a lloproteinase-9/MMP-9 and dipeptidylpeptidase IV/DPPIV/CD26. The inhibition of proteolytic inactivation was functionally measured by receptor-mediated effects, including intracellular calcium mobilization, ERK1/2 phosphorylation, receptor internalization and chemotaxis of CXCR4-positive cells. Protection of SDF-1/CXCL12 against proteolysis was dependent on electrostatic COAM-SDF-1 interactions. By in vivo experiments in mice, we showed that the combination of COAM with SDF-1 delivered through physiological fibrin hydrogel had beneficial effect for the healing of skin wounds. Collectively, we show that COAM protects SDF-1 from proteolytic inactivation, maintaining SDF-1 biological activities. Thus, protection from proteolysis by COAM represents a therapeutic strategy to prolong SDF-1 bioavailability for wound healing applications. [ABSTRACT FROM AUTHOR]

Neutrophils are the first leukocytes to be recruited to sites of inflammation in response to chemotactic factors released by activated macrophages and pulmonary epithelial and endothelial cells in bacterial pneumonia, a common cause of acute respiratory distress syndrome (ARDS). Although neutrophilic inflammation facilitates the elimination of pathogens, neutrophils also may cause bystander tissue injury. Even though the presence of neutrophils in alveolar spaces is a key feature of acute lung injury and ARDS especially from pneumonia, their contribution to the pathogenesis of lung injury is uncertain. The goal of this study was to elucidate the role of neutrophils in a clinically relevant model of bacterial pneumonia. We investigated the effect of reducing neutrophils in a mouse model of pneumococcal pneumonia treated with antibiotics. Neutrophils were reduced with anti-lymphocyte antigen 6 complex locus G6D (Ly6G) monoclonal antibody 24 h before and immediately preceding infection. Mice were inoculated intranasally with Streptococcus pneumoniae and received ceftriaxone 12 h after bacterial inoculation. Neutrophil reduction in mice treated with ceftriaxone attenuated hypoxemia, alveolar permeability, epithelial injury, pulmonary edema, and inflammatory biomarker release induced by bacterial pneumonia, even though bacterial loads in the distal air spaces of the lung were modestly increased as compared with antibiotic treatment alone. Thus, when appropriate antibiotics are administered, lung injury in the early phase of bacterial pneumonia is mediated in part by neutrophils. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense. NEW & NOTEWORTHY: Neutrophil accumulation is a key feature of ARDS, but their contribution to the pathogenesis is still uncertain. We investigated the effect of reducing neutrophils in a clinically relevant mouse model of pneumococcal pneumonia treated with antibiotics. When appropriate antibiotics were administered, neutrophil reduction with Ly6G antibody markedly attenuated lung injury and improved oxygenation. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense. [ABSTRACT FROM AUTHOR]

This paper is concerned with a cross-diffusion tumor invasion model with double-taxis effect. We first investigate the global existence of classical solutions of this model in two-dimensional space. The essential difficulty lies in the second-level taxis effect of immune cells on tumor cells, where chemotactic factor (tumor cells) exhibit their own taxis behavior, the double-taxis effect makes us have to use more detailed analysis and calculation, and some new estimation techniques are used. Subsequently, we also investigate the stability of some equilibria. For small proliferation coefficient, we prove the global asymptotic stability or local asymptotic stability of a semitrivial equilibrium point. While, for the other equilibria, the stability analysis is complicated even for some special cases, and both the double chemotactic coefficients will affect the stability of the solution. [ABSTRACT FROM AUTHOR]

In recent years, the incidence rate of chronic liver diseases continues to rise, such as chronic hepatitis B, nonalcoholic fatty liver disease, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma, and the age of onset gradually becomes younger. At present, the role of many CC chemokines in chronic liver diseases has been confirmed. This article summarizes the research advances in CC chemokines and their receptors that affect chronic liver diseases in recent years and explore their potential application in chronic liver diseases, so as to provide new ideas for the prevention and treatment of chronic liver diseases. [ABSTRACT FROM AUTHOR]

Introduction: Cells expressing taste signaling elements in non-gustatory tissues have been described as solitary chemosensory cells (SCCs) or tuft cells. These "taste-like" cells play a critical role in the maintenance of tissue homeostasis. Although the expression of SCC markers and taste signaling constituents has been identified in mouse gingivae, their role in periodontal homeostasis is still unclear. Methods: Public RNA sequencing datasets were re-analyzed and further validated with RT-PCR/qRT-PCR and immunofluorescent staining to explore the expression of TAS2Rs and downstream signaling constituents in mouse gingival fibroblasts (MGFs). The specific action of salicin on MGFs via Tas2r143 was validated with RNA silence, heterologous expression of taste receptor/Ga-gustducin and calcium imaging. The anti-inflammatory effects of salicin against LPS-induced MGFs were investigated in cell cultures, and were further validated with a ligatureinduced periodontitis mouse model using Ga-gustducin-null (Gnat3-/-) mice. Results: The expression of Tas2r143, Gnat3, Plcb2, and TrpM5 was detected in MGFs. Moreover, salicin could activate Tas2r143, elicited taste signaling and thus inhibited LPS-induced chemokines expression (CXCL1, CXCL2, and CXCL5) in MGFs. Consistently, salicin-treatment inhibited periodontal bone loss, inflammatory/chemotactic factors expression, and neutrophil infiltration in periodontitis mice, while these effects were abolished in Gnat3-/- mice. Discussion: Gingival fibroblasts play a critical role in the maintenance of periodontal homeostasis via "SCC-like" activity. Salicin can activate Tas2r143- mediated bitter taste signaling and thus alleviate periodontitis in mouse, indicating a promising approach to the resolution of periodontal inflammation via stimulating the "SCC-like" function of gingival fibroblasts. [ABSTRACT FROM AUTHOR]

Introduction: The microbial community plays a crucial role in the pathological microenvironment. However, the structure of the microbial community within endometriotic lesions and its impact on the microenvironment is still limited. Methods: All 55 tissue samples, including ovarian ectopic (OEMs) and normal (NE) endometrium, were subjected to 16S rRNA sequencing, metabolomic and proteomic analysis. Results: We found the abundance of Tuzzerella is significantly lower in OEMs compared to NE tissue (p < 0.01). We selected samples from these two groups that exhibited the most pronounced difference in Tuzzerella abundance for further metabolomic and proteomic analysis. Our findings indicated that endometriotic lesions were associated with a decrease in l-Glutamine levels. However, proteomic analysis revealed a significant upregulation of proteins related to the complement pathway, including C3, C7, C1S, CLU, and A2M. Subsequent metabolic and protein correlation predictions demonstrated a negative regulation between l-Glutamine and C7. In vitro experiments further confirmed that high concentrations of Glutamine significantly inhibit C7 protein expression. Additionally, immune cell infiltration analysis, multiplex immunofluorescence, and multifactorial testing demonstrated a positive correlation between C7 expression and the infiltration of regulatory T cells (Tregs) in ectopic lesions, while l-Glutamine was found to negatively regulate the expression of chemotactic factors for Tregs. Conclusion: In this study, we found a clear multi-omics pathway alteration, "Tuzzerella (microbe)—l-Glutamine (metabolite)—C7 (protein)," which affects the infiltration of Tregs in endometriotic lesions. Our findings provide insights into endometriosis classification and personalized treatment strategies based on microbial structures. [ABSTRACT FROM AUTHOR]

In this work, we investigate the existence and non-existence of traveling wave solutions for a chemotaxis model with two chemoattractants. To prove our main results, we apply the dynamical systems theory by constructing a positively invariant set in the four-dimensional space. Particularly, we analyze the monotonicity of traveling wave solutions. [ABSTRACT FROM AUTHOR]

Objectives: Previous observational studies have indicated correlations between various inflammatory cytokines and functional outcomes following ischemic stroke (IS); however, the causality remains unclear. We aimed to further evaluate the causal association between 41 circulating inflammatory cytokines and functional outcomes following IS. Methods: Two‐sample bidirectional Mendelian randomization (MR) analysis was used in this study. The genetic variation of 41 circulating inflammatory cytokines were derived from genome‐wide association study (GWAS) data of European ancestry (n = 8293). The corresponding genetic association of functional outcomes following IS were derived from European ancestry GWAS data (n = 6021). Results: Inverse variance weighted (IVW) analysis showed that genetically predicted increased levels of regulation and activation in normal T‐cell expression and secretion factor (RANTES/CCL5) and eosinophilic chemotactic factor (EOTAXIN/CCL11) were positively correlated with the increased adverse functional outcomes (modified Rankin Scale [mRS≥3] following IS (OR: 1.40, 95% CI: 1.002–1.96, p = 0.049; OR: 1.33, 95% CI: 1.15–1.54, p = 0.0001). Interleukin 18 (IL‐18) level might be the downstream consequence of adverse functional outcomes following IS (β: −0.09, p = 0.039). Other inflammatory cytokines and functional outcomes following IS did not appear to be causally related. Conclusions: This study suggests a causality between inflammation and adverse functional outcomes following IS. RANTES (CCL5) and EOTAXIN (CCL11) may be the upstream factors of adverse functional outcomes following IS, while IL‐18 may be the downstream effect of adverse functional outcomes following IS. Whether these cytokines can be used to predict or improve adverse functional outcomes after IS requires further researches. [ABSTRACT FROM AUTHOR]

Objective To explore the correlation of serum Chemerin level with disease activity and the ratio of T helper 17/regulatory T cells (Th17/Treg) in patients with rheumatoid arthritis (RA). Methods A total of 180 patients with RA who were admitted to our hospital were regarded as the observation group. According to the DAS28 score, the observation group was divided into the high activity group (60 cases), the moderate activity group (60 cases) and the low activity group (60 cases). Another 180 healthy people who underwent physical examination in our hospital during the same period were regarded as the control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of Chemerin, interleukin-9 (IL-9), interleukin-10 (IL-10) and interleukin-17 (IL-17). Flow cytometry was used to detect the Th17/Treg ratio. Spearman correlation analysis was applied to analyze the correlation between serum Chemerin level and DAS28 score. Pearson correlation analysis was used to analyze the correlation between serum Chemerin level and Th17, Treg cell percentage and Th17/Treg ratio. Results The results of this study showed that the serum level of Chemerin was higher in the observation group than that in the control group (P＜0.05). The serum Chemerin level was positively correlated with DAS28 score (P＜0.05). Serum Chemerin levels and DAS28 scores decreased in turn in the high, moderate and low activity groups (P＜0.05). The percentage of Th17 cells and the ratio of Th17/Treg were higher in the observation group than those in the control group, and the percentage of Treg cells was lower in the observation group than that in the control group (P＜ 0.05). The level of IL-10 was lower in the observation group than that in the control group, while levels of IL-17 and IL-9 were higher in the observation group than those in the control group (P＜0.05). The results of Pearson correlation analysis showed that serum Chemerin level was positively correlated with the percentage of Th17 cells and the ratio of Th17/Treg, and negatively correlated with the percentage of Treg cells (P＜0.05). Conclusion Serum Chemerin level is elevated in patients with RA, which is closely related to disease activity and Th17/Treg ratio. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) leads to brain damage, comprising both immediate primary damage and a subsequent cascade of secondary injury mechanisms. The primary injury results in localized brain damage, while the secondary damage initiates inflammatory responses, followed by the disruption of the blood-brain barrier, infiltration of peripheral blood cells, brain edema, and the release of various immune mediators, including chemotactic factors and interleukins. TBI disrupts molecular signaling, cell structures, and functions. In addition to physical tissue damage, such as axonal injuries, contusions, and haemorrhages, TBI interferes with brain functioning, impacting cognition, decision-making, memory, attention, and speech capabilities. Despite a deep understanding of the pathophysiology of TBI, an intensive effort to evaluate the underlying mechanisms with effective therapeutic interventions is imperative to manage the repercussions of TBI. Studies have commenced to explore the potential of employing natural compounds as therapeutic interventions for TBI. These compounds are characterized by their low toxicity and limited interactions with conventional drugs. Moreover, many natural compounds demonstrate the capacity to target various aspects of the secondary injury process. While our understanding of the pathophysiology of TBI, there is an urgent need for effective therapeutic interventions to mitigate its consequences. Here, we aimed to summarize the mechanism of action and the role of phytochemicals against TBI progression. This review discusses the therapeutic implications of various phytonutrients and addresses primary and secondary consequences of TBI. In addition, we highlighted the roles of emerging phytochemicals as promising candidates for therapeutic intervention of TBI. The review highlights the neuroprotective roles of phytochemicals against TBI and the mechanistic approach. Furthermore, our efforts focused on the underlying mechanisms, providing a better understanding of the therapeutic potential of phytochemicals in TBI therapeutics. [ABSTRACT FROM AUTHOR]

SLC7A11 has significant translational value in cancer treatment. However, there are few studies on whether SLC7A11 affects the immune status of lung adenocarcinoma (LUAD). Information on SLC7A11 expression and its impact on prognosis was obtained from the cancer genome atlas and gene expression omnibus databases. The differentially expressed genes (DEGs) were analysed by GO and KEGG. GSEA enrichment analysis was performed in the SLC7A11-high and SLC7A11-low groups. The relationship between SLC7A11 and tumour immunity, immune checkpoints, and immune cell infiltration was studied using R language. We analysed the correlation between SLC7A11 and chemotactic factors (CFs) and chemokine receptors using the TISIDB database. SLC7A11 is overexpressed in many tumours, including LUAD. The 5-year overall survival of patients in the SLC7A11-high group was lower than in the SLC7A11-low group. KEGG analysis found that the DEGs were enriched in ferroptosis signaling pathways. GSEA analysis found that the survival-related signaling pathways were enriched in the SLC7A11-low group. The SLC7A11-low group had higher immune scores and immune checkpoint expression. SLC7A11 was negatively correlated with many immune cells (CD8+ T cells, immature dendritic cells), CFs, chemokine receptors (such as CCL17/19/22/23, CXCL9/10/11/14, CCR4/6, CX3CR1, CXCR3) and MHCs (major histocompatibility complex). SLC7A11 may regulate tumour immunity and could be a potential therapeutic target for LUAD. [ABSTRACT FROM AUTHOR]

Macrophages play a pivotal role in the process of healing burns. One of the major risks in the course of burn healing, in the absence of regenerating epidermis, is infections, which greatly contribute to morbidity and mortality in such patients. Therefore, it is widely agreed that accelerating the recruitment of macrophages into burns may contribute to faster regeneration of the epidermis, thus decreasing the risk of infections. This review describes a unique method for the rapid recruitment of macrophages into burns and the activation of these macrophages to mediate accelerated regrowth of the epidermis and healing of burns. The method is based on the application of bio-degradable "α-gal" nanoparticles to burns. These nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R), which bind the abundant natural anti-Gal antibody that constitutes ~1% of immunoglobulins in humans. Anti-Gal/α-gal nanoparticle interaction activates the complement system, resulting in localized production of the complement cleavage peptides C5a and C3a, which are highly effective chemotactic factors for monocyte-derived macrophages. The macrophages recruited into the α-gal nanoparticle-treated burns are activated following interaction between the Fc portion of anti-Gal coating the nanoparticles and the multiple Fc receptors on macrophage cell membranes. The activated macrophages secrete a variety of cytokines/growth factors that accelerate the regrowth of the epidermis and regeneration of the injured skin, thereby cutting the healing time by half. Studies on the healing of thermal injuries in the skin of anti-Gal-producing mice demonstrated a much faster recruitment of macrophages into burns treated with α-gal nanoparticles than in control burns treated with saline and healing of the burns within 6 days, whereas healing of control burns took ~12 days. α-Gal nanoparticles are non-toxic and do not cause chronic granulomas. These findings suggest that α-gal nanoparticles treatment may harness anti-Gal for inducing similar accelerated burn healing effects also in humans. [ABSTRACT FROM AUTHOR]

Background: Membranous nephropathy (MN) is a major pattern of nephrotic syndrome (NS) in adults. Some MN have secondary causes and some may be accompanied with other glomerular diseases. MN patients coexisting with amyloidosis are very rare, and mostly was polytypic MN. Herein, we describe the first report which identifying monotype PLA2R-MN (κ light chain) concurrent with leukocyte chemotactic factor 2 amyloidosis (ALECT2). This rare case highlights the importance of renal pathology for diagnosis. Case presentation: We describe a case of a 60-year-old male patient with persistent proteinuria and low serum albumin for nine months. No monoclonal component was revealed by serum and urine immunofixation electrophoresis but serum PLA2R antibody was positive. The patient was empirically treated with Leflunomide and Losartan, but edema was not improved. The diagnosis of renal pathology is PLA2R-related monotypic (IgG-κ positive) MN concurrent with ALECT2. Methylprednisolone, cyclosporine A and anticoagulant (rivaroxaban) were prescribed resulting in a complete remission of NS. Conclusions: MN patients concurrent with ALECT2 presented massive proteinuria or NS. When nephrotic range proteinuria is present in ALECT2, it is important to consider that it may be due to a concomitant underlying nephropathy especially MN and treated according to MN will get good therapeutic effect. [ABSTRACT FROM AUTHOR]

Chemotaxis, the guided motion of cells by chemical gradients, plays a crucial role in many biological processes. In the social amoeba Dictyostelium discoideum, chemotaxis is critical for the formation of cell aggregates during starvation. The cells in these aggregates generate a pulse of the chemoattractant, cyclic adenosine 3,5-monophosphate (cAMP), every 6 min to 10 min, resulting in surrounding cells moving toward the aggregate. In addition to periodic pulses of cAMP, the cells also secrete phosphodiesterase (PDE), which degrades cAMP and prevents the accumulation of the chemoattractant. Here we show that small aggregates of Dictyostelium can disperse, with cells moving away from instead of toward the aggregate. This surprising behavior often exhibited oscillatory cycles of motion toward and away from the aggregate. Furthermore, the onset of outward cell motion was associated with a doubling of the cAMP signaling period. Computational modeling suggests that this dispersal arises from a competition between secreted cAMP and PDE, creating a cAMP gradient that is directed away from the aggregate, resulting in outward cell motion. The model was able to predict the effect of PDE inhibition as well as global addition of exogenous PDE, and these predictions were subsequently verified in experiments. These results suggest that localized degradation of a chemoattractant is a mechanism for morphogenesis.

Background: This study targeted at developing a robust, prognostic signature based on super-enhancer-related genes (SERGs) to reveal survival prognosis and immune microenvironment of breast cancer. Methods: RNA-sequencing data of breast cancer were retrieved from The Cancer Genome Atlas (TCGA), 1069 patients of which were randomly assigned into training or testing set in 1:1 ratio. SERGs were downloaded from Super-Enhancer Database (SEdb). After which, a SERGs signature was established based on the training set, with its prognostic value further validated in the testing set. Subsequently, we identified the potential function enrichment and tumor immune infiltration of the model. Moreover, in vitro experiments were completed to further explore the biological functions of ZIC2 gene (one of the risk genes in the prognostic model) in breast cancer. Results: A risk score system of prognostic value was constructed with 6 SERGs (ZIC2, NFE2, FOXJ1, KLF15, POU3F2 and SPIB) to find patients in high-risk group with significantly worse prognosis in both training and testing sets. In addition, a multivariate regression was established via integrating the 6 genes with age and N stage, indicating well performance by calibration, time-dependent receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). Further analysis demonstrated that tumor-associated pathological processes and pathways were significantly enriched in the high-risk group. In general, the novel SERGs signature could be applied to screen breast cancer with immunosuppressive microenvironment for the risk score was negatively correlated with ESTIMATE score, tumor-infiltration lymphocytes (such as CD4 + and CD8 + T cell), immune checkpoints and chemotactic factors. Furthermore, down-regulation of ZIC2 gene expression inhibited the cell viability, cellular migration and cell cycle of breast cancer cells. Conclusions: The novel SERGs signature could predict the prognosis of breast cancer; and SERGs might serve as potential therapeutic targets for breast cancer. [ABSTRACT FROM AUTHOR]

Summary: Leukotriene B4 (LTB4) was recognized as an arachidonate‐derived chemotactic factor for inflammatory cells and an important drug target even before the molecular identification of its receptors. We cloned the high‐ and low‐affinity LTB4 receptors, BLT1 and BLT2, respectively, and examined their functions by generating and studying gene‐targeted mice. BLT1 is involved in the pathogenesis of various inflammatory and immune diseases, including asthma, psoriasis, contact dermatitis, allergic conjunctivitis, age‐related macular degeneration, and immune complex‐mediated glomerulonephritis. Meanwhile, BLT2 is a high‐affinity receptor for 12‐hydroxyheptadecatrienoic acid, which is involved in the maintenance of dermal and intestinal barrier function, and the acceleration of skin and corneal wound healing. Thus, BLT1 antagonists and BLT2 agonists are promising candidates in the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

In this paper, we define an intraguild predation model of one-resource and two-predator, in which the mesopredator catched by a top predator, feeds on a resource that grows according to a logistic growth law; for both the meso and the top predator, Holling type II functional responses are considered. Predators and prey diffuse into a connected bounded region in R². Two scenarios are considered: 1. As a defense mechanism, the resource attracts the top predator that feeds on the mesopredator; 2. The top predator in search of food moves towards areas where the mesopredator population is increasing. Some general properties of the solutions of the model are proved. In addition, the results of the numerical simulations carried out to analyze the effect on the spatial distribution of the populations of the indirect defense mechanism of the first scenario are shown. This is contrasted with the results of the model simulations corresponding to the second scenario, in which the diffusion of the top predator is regulated by a tendency to move towards the mesopredator gradient. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the relationship between gestational diabetes mellitus (GDM) and Chemerin by analyzing chemerin levels in peripheral blood and cord blood, and chemerin mRNA and its protein expression in placenta and adipose tissue.Methods: A case-control study was conducted in 110 women with GDM and 110 controls without GDM who received regular prenatal services and delivered at Shanghai Pudong New Area Healthcare Hospital for Women and Children from June 2019 to December 2020.Results: The age, pre-pregnancy weight, pre-pregnancy BMI, antepartum BMI, TG/HDL ratio and TG levels in pregnant women with GDM were significantly higher than those in women without GDM, and HDL levels were significantly lower than those in the normal group. Chemerin in the umbilical cord blood of the GDM group was significantly higher than in that of the normal group, but there was no difference in chemerin levels in peripheral blood. In the two groups, the chemerin concentration in peripheral blood was significantly higher than that in umbilical cord blood (P< 0.001). The Chemerin mRNA and protein expression levels in the placenta and adipose tissue of pregnant women in the GDM group were significantly higher than those in the normal group (P < 0.001). In the GDM group, the expression of chemerin protein in adipose tissue was significantly higher than that in placental tissue. Regression analysis showed that the expression level of chemerin protein in placental tissue and adipose tissue was positively correlated with the risk of GDM.Conclusion: Elevated chemerin is closely related to the risk of GDM, and the placenta may be an important secretion of chemotactic factor sources in addition to adipose tissue and participate in the development of GDM. [ABSTRACT FROM AUTHOR]

Background: Atrophic rhinitis is a chronic debilitating nasal disease which may be primary, or secondary to various underlying etiologies. Several methods of treatment have been previously adopted with minimal success rate. In order to achieve effective and long-standing method of treatment for this challenging pathology, this method should work mainly on reversal of the pathologic changes in nasal microanatomy. Objective: Review article investigating the use of platelet-rich plasma in treatment of atrophic rhinitis. Methods: We scoured scholarly journals and databases including PubMed, Google Scholar, and Science Direct for reports on Treatment of atrophic rhinitis, Platelet-rich plasma and new biological modality between November 1990 and April 2023. However, only the latest or most comprehensive study was considered. The authors also assessed the usefulness of references drawn from similar books. As a result, non-English documents have been overlooked due to a lack of resources to translate them. It was commonly recognized that scientific research did not include things like unpublished publications, oral presentations, conference abstracts, or dissertations. Conclusion: Platelet Rich Plasma (PRP) is a plasma fraction with a very high platelet content that also contains phagocytic cells, a significant amount of fibrinogen, a number of chemotactic factors and cytokines that may be used to control tissue inflammatory response, as well as growth factors that can help with tissue healing and regeneration. It is now considered the best treatment for treating atrophic rhinitis as a result. [ABSTRACT FROM AUTHOR]

C-C motif ligand 2 (CCL2), also known as monocytic chemotactic protein 1 (MCP-1), is an integral chemotactic factor which recruits macrophages for the immune response. Together with its receptors (e.g., CCR2, ACKR1, and ACKR2), they exert noticeable influences on various diseases of different systems. At the maternal-fetal interface, CCL2 is detected to be expressed in trophoblasts, decidual tissue, the myometrium, and others. Meanwhile, existing reports have determined a series of physiological regulators of CCL2, which functions in maintaining normal recruitment of immunocytes, tissue remodeling, and angiogenesis. However, abnormal levels of CCL2 have also been reported to be associated with adverse pregnancy outcomes such as spontaneous abortion, preeclampsia and preterm labor. In this review, we concentrate on CCL2 expression at the maternal-fetal interface, as well as its precise regulatory mechanisms and classic signaling pathways, to reveal the multidimensional aspects of CCL2 in pregnancy. [ABSTRACT FROM AUTHOR]

Moving cells can sense and respond to physical features of the microenvironment; however, in vivo, the significance of tissue topography is mostly unknown. Here, we used Drosophila border cells, an established model for in vivo cell migration, to study how chemical and physical information influences path selection. Although chemical cues were thought to be sufficient, live imaging, genetics, modeling, and simulations show that microtopography is also important. Chemoattractants promote predominantly posterior movement, whereas tissue architecture presents orthogonal information, a path of least resistance concentrated near the center of the egg chamber. E-cadherin supplies a permissive haptotactic cue. Our results provide insight into how cells integrate and prioritize topographical, adhesive, and chemoattractant cues to choose one path among many.

Background: Breast cancer (BRCA) is the most common malignancy with high morbidity and mortality in women, and transcription factor (TF) is closely related to the occurrence and development of BRCA. This study was designed to identify a prognostic gene signature based on TF family to reveal immune characteristics and prognostic survival of BRCA. Methods: In this study, RNA-sequence with corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and GSE42568. Prognostic differentially expressed transcription factor family genes (TFDEGs) were screened to construct a risk score model, after which BRCA patients were stratified into low-risk and high-risk groups based on their corresponding risk scores. Kaplan–Meier (KM) analysis was applied to evaluate the prognostic implication of risk score model, and a nomogram model was developed and validated with the TCGA and GSE20685. Furthermore, the GSEA revealed pathological processes and signaling pathways enriched in the low-risk and high-risk groups. Finally, analyses regarding levels of immune infiltration, immune checkpoints and chemotactic factors were all completed to investigate the correlation between the risk score and tumor immune microenvironment (TIME). Results: A prognostic 9-gene signature based on TFDEGs was selected to establish a risk score model. According to KM analyses, high-risk group witnessed a significantly worse overall survival (OS) than low-risk group in both TCGA-BRCA and GSE20685. Furthermore, the nomogram model proved great possibility in predicting the OS of BRCA patients. As indicted in GSEA analysis, tumor-associated pathological processes and pathways were relatively enriched in high-risk group, and the risk score was negatively correlated with ESTIMATE score, infiltration levels of CD4+ and CD8+T cells, as well as expression levels of immune checkpoints and chemotactic factors. Conclusions: The prognostic model based on TFDEGs could distinguish as a novel biomarker for predicting prognosis of BRCA patients; in addition, it may also be utilized to identify potential benefit population from immunotherapy in different TIME and predict potential drug targets. [ABSTRACT FROM AUTHOR]

Tumor microparticles (T-MPs) are considered as a tumor vaccine candidate. Although some studies have analyzed the mechanism of T-MPs as tumor vaccine, we still lack understanding of how T-MPs stimulate a strong anti-tumor immune response. Here, we show that T-MPs induce macrophages to release a key chemotactic factor CCL2, which attracts monocytes to the vaccine injection site and enhances endocytosis of antigen. Monocytes subsequently enter the draining lymph node, and differentiate into monocyte-derived DCs (moDCs), which present tumor antigens to T lymphocytes and deliver a potent anti-tumor immune response. Mechanically, T-MPs activate the cGAS-STING signaling through DNA fragments, and then induce monocytes to upregulate the expression of IRF4, which is a key factor for monocyte differentiation into moDCs. More importantly, monocytes that have endocytosed T-MPs acquire the ability to treat tumors. Collectively, this work might provide novel vaccination strategy for the development of tumor vaccines and facilitate the application of T-MPs for clinic oncotherapy. [ABSTRACT FROM AUTHOR]

Collagen‐based scaffolds reveals promising to repair severe skin defects. The mechanical strength of collagen‐based scaffold (CCS) limited its clinical application. Embedding poly(lactic‐co‐glycolic) acid (PLGA) knitted mesh into CCS improves the mechanical strength of the scaffold. This study was conducted to optimize the configuration of PLGA knitted mesh‐collagen‐chitosan scaffold (PCCS), and explore possible mechanisms. PLGA knitted mesh was embedded in CCS through freeze‐drying method. With the PLGA knitted mesh located at the bottom, middle, or both bottom and top layers of the CCS, three kinds of PCCS were developed. A full‐thickness skin wound model was established in Sprague Dawley rats to evaluate the therapeutic effects of different PCCS against CCS. The properties and healing effect of the scaffolds were investigated. Several growth factors and chemotactic factors, that is, VEGF, PDGF, CD31, α‐SMA, TGF‐β1, and TGF‐β3 were analyzed and evaluated. Re‐epithelialization and angiogenesis were observed in all animal groups with the treatment of three kinds of PCCS scaffolds and the CCS scaffold (control). The protein and gene expression of VEGF, PDGF, CD31, α‐SMA, TGF‐β1, and TGF‐β3 showed different dynamics at different time points. Based on the healing effects and the expression of growth factors and chemotactic factors, scaffold with the PLGA knitted mesh located at the bottom layer of the CCS demonstrated the best healing effect and accelerated re‐epithelialization and angiogenesis among all the scaffolds evaluated. PCCS with the PLGA mesh located in the bottom layer of the scaffold accelerated wound healing by creating a more supportive environment for re‐epithelialization and angiogenesis. [ABSTRACT FROM AUTHOR]

Introduction: It has been proven that hydrogen has obvious anti-inflammatory effects in animal experiments and clinical practice. However, the early dynamic process of the inflammatory response caused by lipopolysaccharide (LPS) and the anti-inflammatory effect of hydrogen has not been definitively reported. Methods: Inflammation in male C57/BL6J mice or RAW264.7 cells was induced with LPS, for which hydrogen was immediately administered until samples were taken. Pathological changes in lung tissue were assessed using hematoxylin and eosin (HE) staining. Levels of inflammatory factors in serum were determined using liquid protein chip. The mRNA levels of chemotactic factors in lung tissues, leukocytes, and peritoneal macrophages were measured by qRT-PCR. The expression levels of IL-1a and HIF-1a were measured by immunocytochemistry. Results: Hydrogen alleviated LPS-induced inflammatory infiltration in the lung tissues of mice. Among the 23 inflammatory factors screened, LPS-induced upregulation of IL-1a etc. was significantly inhibited by hydrogen within 1 hour. The mRNA expression of MCP-1, MIP-1α, G-CSF, and RANTES was inhibited obviously by hydrogen at 0.5 and 1 h in mouse peritoneal macrophages. In addition, hydrogen significantly blocked LPS or H2O2-induced upregulation of HIF-1α, and IL-1α in 0.5 h in RAW264.7 cells. Discussion: The results suggested that hydrogen is potentially inhibitive against inflammation by inhibiting HIF-1a and IL-1a release at early occurrence. The target of the inhibitive LPS-induced-inflammatory action of hydrogen is chemokines in macrophages in the peritoneal cavity. This study provides direct experimental evidence for quickly controlling inflammation with the translational application of a hydrogen-assisted protocol. [ABSTRACT FROM AUTHOR]

During pregnancy, maternal blood circulates through the intervillous space of the placenta and the reciprocal interactions between foetal tissues and maternal immune cells makes the intervillous space a unique immunological niche. Labour is characterised by a proinflammatory response in the myometrium, but the relationship between local and systemic changes during the onset of labour remains elusive. We here aimed to investigate how the systemic and intervillous circulatory systems are affected during labour from an immunological point of view. We report that the proportion of monocytes is dramatically higher in peripheral (PB), intervillous blood (IVB) and decidua in labouring (n = 14) compared to non-labouring women (n = 15), suggesting that labour leads to both a systemic and local mobilisation of monocytes. Labour was associated with a relative increase of effector memory T cells in the intervillous space compared to the periphery, and MAIT cells and T cells showed an elevated expression of activation markers both in PB and IVB. Intervillous monocytes consisted to a higher degree of CD14+CD16+ intermediate monocytes compared to peripheral monocytes, independently of mode of delivery, and displayed an altered phenotypic expression pattern. A proximity extension assay analysis of 168 proteins revealed that several proteins associated to myeloid cell migration and function, including CCL2 and M-CSF, were upregulated in IVB plasma in labouring women. Thus, the intervillous space could be a bridging site for the communication between the placenta and the periphery, which contribute to monocyte mobilisation and generation of inflammatory reactions during spontaneous labour. [ABSTRACT FROM AUTHOR]

Summary: Neutrophils or polymorphonuclear neutrophils (PMNs) are an important component of innate host defense. These phagocytic leukocytes are recruited to infected tissues and kill invading microbes. There are several general characteristics of neutrophils that make them highly effective as antimicrobial cells. First, there is tremendous daily production and turnover of granulocytes in healthy adults—typically 1011 per day. The vast majority (~95%) of these cells are neutrophils. In addition, neutrophils are mobilized rapidly in response to chemotactic factors and are among the first leukocytes recruited to infected tissues. Most notably, neutrophils contain and/or produce an abundance of antimicrobial molecules. Many of these antimicrobial molecules are toxic to host cells and can destroy host tissues. Thus, neutrophil activation and turnover are highly regulated processes. To that end, aged neutrophils undergo apoptosis constitutively, a process that contains antimicrobial function and proinflammatory capacity. Importantly, apoptosis facilitates nonphlogistic turnover of neutrophils and removal by macrophages. This homeostatic process is altered by interaction with microbes and their products, as well as host proinflammatory molecules. Microbial pathogens can delay neutrophil apoptosis, accelerate apoptosis following phagocytosis, or cause neutrophil cytolysis. Here, we review these processes and provide perspective on recent studies that have potential to impact this paradigm. [ABSTRACT FROM AUTHOR]

Migratory cells use distinct motility modes to navigate different microenvironments, but it is unclear whether these modes rely on the same core set of polarity components. To investigate this, we disrupted actin-related protein 2/3 (Arp2/3) and the WASP-family verprolin homologous protein (WAVE) complex, which assemble branched actin networks that are essential for neutrophil polarity and motility in standard adherent conditions. Surprisingly, confinement rescues polarity and movement of neutrophils lacking these components, revealing a processive bleb-based protrusion program that is mechanistically distinct from the branched actin-based protrusion program but shares some of the same core components and underlying molecular logic. We further find that the restriction of protrusion growth to one site does not always respond to membrane tension directly, as previously thought, but may rely on closely linked properties such as local membrane curvature. Our work reveals a hidden circuit for neutrophil polarity and indicates that cells have distinct molecular mechanisms for polarization that dominate in different microenvironments.

Helicobacter pylori is a pathogen that chronically colonizes the stomachs of approximately half of the world's population and contributes to the development of gastric inflammation. We demonstrated previously in vivo that H. pylori uses motility to preferentially colonize injury sites in the mouse stomach. However, the chemoreceptor responsible for sensing gastric injury has not yet been identified. In this study, we utilized murine gastric organoids (gastroids) and mutant H. pylori strains to investigate the components necessary for H. pylori chemotaxis. High-intensity 730-nm light (two-photon photodamage) was used to cause single-cell damage in gastroids, and repair of the damage was monitored over time; complete repair occurred within ∼10 min in uninfected gastroids. Wild-type H. pylori accumulated at the damage site after gastric damage induction. In contrast, mutants lacking motility (ΔmotB) or chemotaxis (ΔcheY) did not accumulate at the injury site. Using mutants lacking individual chemoreceptors, we found that only TlpB was required for H. pylori accumulation, while TlpA, TlpC, and TlpD were dispensable. All strains that were able to accumulate at the damage site limited repair. When urea (an identified chemoattractant sensed by TlpB) was microinjected into the gastroid lumen, it prevented the accumulation of H. pylori at damage sites. Overall, our findings demonstrate that H. pylori colonizes and limits repair at damage sites via chemotactic motility that requires the TlpB chemoreceptor to sense signals generated by gastric epithelial cells.

Chemokines (chemotactic cytokines) are involved in a wide variety of biological processes. Following microbial infection, there is often robust chemokine signaling elicited from infected cells, which contributes to both innate and adaptive immune responses that control growth of the invading pathogen. Infection of the central nervous system (CNS) by the neuroadapted John Howard Mueller (JHM) strain of mouse hepatitis virus (JHMV) provides an excellent example of how chemokines aid in host defense as well as contribute to disease. Intracranial inoculation of the CNS of susceptible mice with JHMV results in an acute encephalomyelitis characterized by widespread dissemination of virus throughout the parenchyma. Virus-specific T cells are recruited to the CNS, and control viral replication through release of antiviral cytokines and cytolytic activity. Sterile immunity is not acquired, and virus will persist primarily in white matter tracts leading to chronic neuroinflammation and demyelination. Chemokines are expressed and contribute to defense as well as chronic disease by attracting targeted populations of leukocytes to the CNS. The T cell chemoattractant chemokine CXCL10 (interferon-inducible protein 10 kDa, IP-10) is prominently expressed in both stages of disease, and serves to attract activated T and B lymphocytes expressing CXC chemokine receptor 3 (CXCR3), the receptor for CXCL10. Functional studies that have blocked expression of either CXCL10 or CXCR3 illuminate the important role of this signaling pathway in host defense and neurodegeneration in a model of viral-induced neurologic disease.

During development, lymphatic endothelial cell (LEC) progenitors differentiate from venous endothelial cells only in limited regions of the body. Thus, LEC migration and subsequent tube formation are essential processes for the development of tubular lymphatic vascular network throughout the body. In this review, we discuss chemotactic factors, LEC-extracellular matrix interactions and planar cell polarity regulating LEC migration and formation of tubular lymphatic vessels. Insights into molecular mechanisms underlying these processes will help in understanding not only physiological lymphatic vascular development but lymphangiogenesis associated with pathological conditions such as tumors and inflammation. [ABSTRACT FROM AUTHOR]

Introduction: Cancer is a disease caused by abnormal growth and uncontrolled cells. Moringa leaf extract can prevent or destroy tumors and cancer cells because it contains benzyl isothiocyanate. Many scientific studies have shown that these chemicals have anti-cancer and chemoprotective capabilities. IL-8 is a chemotactic factor expressed in endothelial cells. This study aims to know the potential of Moringa leaf extract as anti-angiogenesis of oral cancer by IL-8 expression in rats induced by benzo(a)pyrene. Material and methods: This research was an experimental laboratory with a post-test only control group design divided into four groups, control group (K) and a treatment group was given Moringa extract with a dose of 20mg/kg/BW, 40mg/kg/BW, 80mg/kg/BW. Immunohistochemical analysis was used to determine IL-8 expression. Result: ANOVA data analysis revealed that group treatment with 40mg/kg/BW has the lowest number of IL-8 expression in endothelial cells of rats induced by benzo(a)pyrene. Conclusion: Moringa oleifera extract with a dose of 40 mg/kg/BW is the best dose that can inhibit angiogenesis of oral cancer cells in male rats (Rattus norvegicus) induced benzo(a)pyrene. [ABSTRACT FROM AUTHOR]

The development of cholestatic liver injury (CLI) involves inflammation, but the dominant pathway mediating the chemotaxis is not yet established. This work explored key signaling pathway mediating chemotaxis in CLI and the role of Kupffer cells in the inflammatory liver injury. Probe inhibitors T-5224 (100 mg/kg) for AP-1 and C188–9 (100 mg/kg) for STAT3 were used to validate key inflammatory pathways in alpha-naphthylisothiocyanate (ANIT, 100 mg/kg)-induced CLI. Two doses of GdCl 3 (10 mg/kg and 40 mg/kg) were used to delete Kupffer cells and explore their role in CLI. Serum and liver samples were collected for biochemical and mechanism analysis. The liver injury in ANIT-treated mice were significantly increased supported by biochemical and histopathological changes, and neutrophils gathering around the necrotic loci. Inhibitor treatments down-regulated liver injury biomarkers except the level of total bile acid. The chemokine Ccl2 increased by 170-fold and to a less degree Cxcl2 by 45-fold after the ANIT treatment. p-c-Jun and p-STAT3 were activated in the group A but inhibited by the inhibitors in western blot analysis. The immunofluorescence results showed AP-1 not STAT3 responded to inhibitors in ANIT-induced CLI. With or without GdCl 3 , there was no significant difference in liver injury among the CLI groups. In necrotic loci in CLI, CXCL2 colocalized with hepatocyte biomarker Albumin, not with the F4/80 in Kupffer cells. Conclusively, AP-1 played a more critical role in the inflammation cascade than STAT3 in ANIT-induced CLI. Hepatocytes, not the Kupffer cells released chemotactic factors mediating the chemotaxis in CLI. [Display omitted] • AP-1 inhibitor T-5224 and STAT3 inhibitor C188-9 deleted cholestatic liver injury respectively. • Activation of AP-1 correlated more to cholestatic liver injury than STAT3. • Chemokines mediating the chemotaxis in cholestatic liver injury was released by hepatocytes not the Kupffer cells. • Kupffer cells in cholestatic liver injury were neither protective nor disruptive. [ABSTRACT FROM AUTHOR]

Objectives: To assess the prevalence of leukocyte cell-derived chemotactic 2 (LECT2), its organ involvement, and its clinical association in autopsies from an ethnically biased population.Methods: The tissues from all autopsies of individuals diagnosed with amyloidosis were reassessed and typed for amyloid light chain (AL) amyloidosis, amyloid A (AA) amyloidosis, transthyretin amyloidosis (ATTR), and leukocyte chemotactic factor 2 amyloidosis (ALECT2) by immunohistochemistry. Organ involvement was described and correlated with its clinical associations.Results: Of 782 autopsies, 27 (3.5%) had a confirmed diagnosis of amyloidosis. Of these, 14 (52%) corresponded to ALECT2, 5 (19%) to AL amyloidosis, 2 (7%) to ATTR amyloidosis, 1 (4%) to AA amyloidosis, and 5 (21%) as undetermined-type amyloidosis. The LECT2 amyloid deposits were found in the kidneys, liver, spleen, and adrenal glands in most individuals. Except for the kidneys, there were no clinical signs suggestive of amyloid deposition in most of the affected organs. LECT2 amyloidosis was not associated with the cause of death in any case. No cases had heart or brain involvement. Potential subclinical effects of amyloid deposition in organs such as adrenal glands and spleen require further study.Conclusions: This autopsy study confirms the high prevalence of LECT2 amyloidosis in the Mexican population, with frequent amyloid deposition in the kidneys, liver, spleen, and adrenal glands. [ABSTRACT FROM AUTHOR]

Bacteria or viral outbreaks can cause tilapia hemorrhage, ensuring considerable volume of hemoglobin (Hb) into the tissue. However, the hemoglobin toxicity on tissue and high doses also effect on tissue this phenomena is still under consideration. Therefore, current study exploited Nile tilapia kidney (NTK) cells to deeply expose the toxic effect of Hb on NTK cells. Toxicity of Hb on NTK cells was determined in terms of cells growth, expression of iron metabolism and inflammation-related genes, consequently examined antioxidant-related enzymes genes expression, intracellular iron and reactive oxygen species (ROS) contents, and apoptosis-related genes expression. The results showed that Hb and heme significantly inhibited NTK cells growth and up-regulated iron metabolism-related genes expression in different degrees. The Hb and heme activated the expression of pro-inflammatory cytokines (TNF-α, tumor necrosis factor-α; IL-1β, interleukin 1β; IL-6, interleukin 6), the anti-inflammatory factor (IL-10, interleukin 10) and the chemotactic factors (IL-4, interleukin 4; IL-8, interleukin 8) through NF-κB pathway, meanwhile activated the expression of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). Moreover, the Hb significantly increased intracellular iron and ROS contents while the expression of apoptosis-related genes was significantly activated by both Hb and heme. Current investigation suggested that high oxidative activity of Hb could activate iron metabolism- and inflammation-related genes expression, and increase intracellular iron and ROS levels, lead to up-regulated the expression of apoptosis genes in NTK cells. • Hb promoted the expression of inflammation-related genes. • Hb activated the expression of genes related to iron metabolism. • Hb enhanced the expression of antioxidant-related genes. • Hb increased intracellular iron and ROS contents. • Hb activated the expression of apoptosis-related genes. [ABSTRACT FROM AUTHOR]

To study the dynamics and mechanisms controlling activation of the heterotrimeric G protein Gα2βγ in Dictyostelium in response to stimulation by the chemoattractant cyclic AMP (cAMP), we monitored the G protein subunit interaction in live cells using bioluminescence resonance energy transfer (BRET). We found that cAMP induces the cAR1-mediated dissociation of the G protein subunits to a similar extent in both undifferentiated and differentiated cells, suggesting that only a small number of cAR1 (as expressed in undifferentiated cells) is necessary to induce the full activation of Gα2βγ. In addition, we found that treating cells with caffeine increases the potency of cAMP-induced Gα2βγ activation; and that disrupting the microtubule network but not F-actin inhibits the cAMP-induced dissociation of Gα2βγ. Thus, microtubules are necessary for efficient cAR1-mediated activation of the heterotrimeric G protein. Finally, kinetics analyses of Gα2βγ subunit dissociation induced by different cAMP concentrations indicate that there are two distinct rates at which the heterotrimeric G protein subunits dissociate when cells are stimulated with cAMP concentrations above 500 nM versus only one rate at lower cAMP concentrations. Quantitative modeling suggests that the kinetics profile of Gα2βγ subunit dissociation results from the presence of both uncoupled and G protein pre-coupled cAR1 that have differential affinities for cAMP and, consequently, induce G protein subunit dissociation through different rates. We suggest that these different signaling kinetic profiles may play an important role in initial chemoattractant gradient sensing.

Metastasis remains the greatest challenge in the clinical management of cancer. Cell motility is a fundamental and ancient cellular behaviour that contributes to metastasis and is conserved in simple organisms. In this Review, we evaluate insights relevant to human cancer that are derived from the study of cell motility in non-mammalian model organisms. Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster and Danio rerio permit direct observation of cells moving in complex native environments and lend themselves to large-scale genetic and pharmacological screening. We highlight insights derived from each of these organisms, including the detailed signalling network that governs chemotaxis towards chemokines; a novel mechanism of basement membrane invasion; the positive role of E-cadherin in collective direction-sensing; the identification and optimization of kinase inhibitors for metastatic thyroid cancer on the basis of work in flies; and the value of zebrafish for live imaging, especially of vascular remodelling and interactions between tumour cells and host tissues. While the motility of tumour cells and certain host cells promotes metastatic spread, the motility of tumour-reactive T cells likely increases their antitumour effects. Therefore, it is important to elucidate the mechanisms underlying all types of cell motility, with the ultimate goal of identifying combination therapies that will increase the motility of beneficial cells and block the spread of harmful cells.

Chronic endometritis (CE) is a chronic and persistent inflammation condition of endometrium, mainly caused by pathogen infection. It is potentially associated with infertility and poor reproductive outcomes. Although the pregnancy outcomes of some CE patients have been greatly improved after antibiotic treatment at present, the persistent CE is still a thorny problem in other patients, because the etiology of persistent CE is still unknown and the treatment effect is poor. More and more studies have suggested that the immune status of the endometrium in CE patients has changed, which is involved in the pathological process contributing to the reduced endometrial receptivity and adverse pregnancy outcomes. The changes of endometrial immune state in CE patients are mainly manifested as the number alterations of both innate immunocytes represented by uterine natural killer cells (uNK cells) and macrophages and adaptive immunocytes represented by B cells and CD4+T cells, the dysregulated proportion of CD4+T immune cell subsets and abnormal expression of cytokines and chemokines. In this artile, we reviewed the research progresses of endometrial immune state changes of CE, so as to gain further insights into the pathological characteristics and the internal mechanism that possibly affects the pregnancy outcomes of women with CE from the immune perspective. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the levels of YKL-40 during and after coronary artery bypass grafting surgery (CABG) and to establish possible connections between YKL-40 and markers of oxidative stress, inflammation, and myocardial injury. Patients undergoing elective CABG utilizing cardiopulmonary bypass (CPB) were recruited into the study. Blood samples were collected at the onset of anesthesia, during surgery and post-operatively. Levels of YKL-40, 8-isoprostane, interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and troponin T (TnT) were measured by immunoassay. YKL-40 levels increased significantly 24 h after CPB. Positive correlation was seen between post-operative TnT and YKL-40 levels (r = 0.457, p = 0.016) and, interestingly, baseline YKL-40 predicted post-operative TnT increase (r = 0.374, p = 0.050). There was also a clear association between YKL-40 and the chemotactic factors MCP-1 (r = 0.440, p = 0.028) and IL-8 (r = 0.484, p = 0.011) linking YKL-40 to cardiac inflammation and fibrosis following CABG. The present results show, for the first time, that YKL-40 is associated with myocardial injury and leukocyte-activating factors following coronary artery bypass surgery. YKL-40 may be a factor and/or biomarker of myocardial inflammation and injury and subsequent fibrosis following heart surgery. [ABSTRACT FROM AUTHOR]

Triggering receptor expressed on myeloid cell-2 (TREM2) is a transmembrane receptor which is specifically expressed on myeloid cells. To date, TREM2 has been confirmed as a key factor in many pathologies, such as Alzheimer's disease, obesity-related metabolic syndrome, fatty liver and atherosclerosis. However, the role of TREM2 in tumors remains poorly understood. TREM2 is highly expressed in more than 200 primary and metastatic tumors, a feature that makes TREM2 a potential clinical target for tumor immunotherapy. The tumor microenvironment (TME) is the "soil" which tumors survive on and exhibits immunosuppressive characteristics. During the development of a tumor, TME will secrete various chemotactic factors to recruit myeloid cells. It is clear now that cancer progression and metastasis depend on the interactions between cancer cells and myeloid cell infiltration in TME. As an important receptor involved in inflammatory suppression signaling pathways, TREM2 may play an important role in immune escape by the tumor. Recently, several studies have illustrated that TREM2 expressed on tumor infiltrated myeloid cells acts as a crucial regulator of the antitumor immune response. In this review, we systematically summarize recent publications about the latest advances in knowledge of TREM2 in cancer, especially focusing on its role in tumor associated myeloid cells and tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is the most common type of degenerative arthritis and affects the entire joint, causing pain, joint inflammation, and cartilage damage. Various risk factors are implicated in causing OA, and in recent years, a lot of research and interest have been directed toward chronic low-grade inflammation in OA. Monocyte chemoattractant protein-1 (MCP-1; also called CCL2) acts through C-C chemokine receptor type 2 (CCR2) in monocytes and is a chemotactic factor of monocytes that plays an important role in the initiation of inflammation. The targeting of CCL2-CCR2 is being studied as part of various topics including the treatment of OA.Methods: In this study, we evaluated the potential therapeutic effects the sCCR2 E3 gene may exert on OA. The effects of sCCR2 E3 were investigated in animal experiments consisting of intra-articular injection of sCCR2 E3 in a monosodium iodoacetate (MIA)-induced OA rat model. The effects after intra-articular injection of sCCR2 E3 (fusion protein encoding 20 amino acids of the E3 domain of the CCL2 receptor) in a monosodium iodoacetate-induced OA rat model were compared to those in rats treated with empty vector (mock treatment) and full-length sCCR2.Results: Pain improved with expression of the sCCR2 gene. Improved bone resorption upon sCCR2 E3 gene activation was confirmed via bone analyses using micro-computed tomography. Histologic analyses showed that the sCCR2 E3 gene exerted protective effects against cartilage damage and anti-inflammatory effects on joints and the intestine.Conclusions: These results show that sCCR2 E3 therapy is effective in reducing pain severity, inhibiting cartilage destruction, and suppressing intestinal damage and inflammation. Thus, sCCR2 E3 may be a potential therapy for OA. [ABSTRACT FROM AUTHOR]

Few cytokines/growth modulating proteins are known to be chemoattractants for hematopoietic stem (HSC) and progenitor cells (HPC); stromal cell‐derived factor 1α (SDF1α/CXCL12) being the most potent known such protein. DEK, a nuclear DNA‐binding chromatin protein with hematopoietic cytokine‐like activity, is a chemotactic factor attracting mature immune cells. Transwell migration assays were performed to test whether DEK serves as a chemotactic agent for HSC/HPC. DEK induced dose‐ and time‐dependent directed migration of lineage negative (Lin–) Sca‐1+ c‐Kit+ (LSK) bone marrow (BM) cells, HSCs and HPCs. Checkerboard assays demonstrated that DEK's activity was chemotactic (directed), not chemokinetic (random migration), in nature. DEK and SDF1α compete for HSC/HPC chemotaxis. Blocking CXCR2 with neutralizing antibodies or inhibiting Gαi protein signaling with Pertussis toxin pretreatment inhibited migration of LSK cells toward DEK. Thus, DEK is a novel and rare chemotactic agent for HSC/HPC acting in a direct or indirect CXCR2 and Gαi protein‐coupled signaling‐dependent manner. [ABSTRACT FROM AUTHOR]

Leukocyte chemotactic factor 2-associated (ALECT2) amyloidosis is one of the recently reported types of amyloidosis, which is caused by the extracellular deposition of leukocyte chemotactic factor 2 (LECT2). There have not been any reports involving the concurrence of ALECT2 amyloidosis with Sjögren's syndrome (SS) or systemic lupus erythematosus (SLE)s. Herein, we report a case of a 68-year-old Chinese woman presenting with long duration of sicca symptoms. The clinical evaluation and laboratory findings showed that she had SS overlapped with SLE. Kidney biopsy revealed a membranoproliferative glomerulonephritis (MPGN) with glomerular deposition of dominant IgG3-kappa by immunofluorescene, which was related to SS/SLE. Furthermore, patchy congophilic amyloid deposits in the tubulointerstitium were detected, which were positive for LECT2 protein by immunohistochemical staining and immunoelectron microscopy. This is the first case of ALECT2 amyloidosis that coexisted with SS/SLE, and the causal relationship between ALECT2 amyloidosis and autoimmune diseases remain unclear. [ABSTRACT FROM AUTHOR]

Alveolar organoids (AOs), derived from human pluripotent stem cells (hPSCs) exhibit lung-specific functions. Therefore, the application of AOs in pulmonary disease modeling is a promising tool for understanding disease pathogenesis. However, the lack of immune cells in organoids limits the use of human AOs as models of inflammatory diseases. In this study, we generated AOs containing a functional macrophage derived from hPSCs based on human fetal lung development using biomimetic strategies. We optimized culture conditions to maintain the iMACs (induced hPSC-derived macrophages) AOs for up to 14 days. In lipopolysaccharide (LPS)-induced inflammatory conditions, IL-1β, MCP-1 and TNF-α levels were significantly increased in iMAC-AOs, which were not detected in AOs. In addition, chemotactic factor IL-8, which is produced by mononuclear phagocytic cells, was induced by LPS treatment in iMACs-AOs. iMACs-AOs can be used to understand pulmonary infectious diseases and is a useful tool in identifying the mechanism of action of therapeutic drugs in humans. Our study highlights the importance of immune cell presentation in AOs for modeling inflammatory pulmonary diseases. [ABSTRACT FROM AUTHOR]

The rapid clearance of apoptotic cells (ACs), known as efferocytosis, prompts the inhibition of inflammatory responses and autoimmunity and maintains homeostatic cell turnover by controlling the release of intracellular contents. The fast clearance of ACs requires professional and nonprofessional phagocytic cells that can accurately and promptly recognize ACs and migrate towards them. Cells undergoing apoptosis alarm their presence by releasing special soluble chemotactic factors, such as lactoferrin, that act as "Find me," "Keep out," or "Stay away" signals to recruit phagocytic cells, such as macrophages or prevent granulocyte migration. Efferocytosis effectively serves to prevent damage‐associated molecular pattern release and secondary necrosis and inhibit inflammation/autoimmunity at the very first step. Since less attention has been given to the cross‐talk and balance of "Find me" and "Keep out" signals released from ACs in efferocytosis, we set out to investigate the current knowledge of the roles of "Find me" and "Keep out" signals in the efferocytosis process. [ABSTRACT FROM AUTHOR]

The kidney has tremendous capacity to repair after acute injury, however, pathways guiding adaptive and fibrotic repair are poorly understood. We developed a model of adaptive and fibrotic kidney regeneration by titrating ischemic injury dose. We performed detailed biochemical and histological analysis and profiled transcriptomic changes at bulk and single-cell level (> 110,000 cells) over time. Our analysis highlights kidney proximal tubule cells as key susceptible cells to injury. Adaptive proximal tubule repair correlated with fatty acid oxidation and oxidative phosphorylation. We identify a specific maladaptive/profibrotic proximal tubule cluster after long ischemia, which expresses proinflammatory and profibrotic cytokines and myeloid cell chemotactic factors. Druggability analysis highlights pyroptosis/ferroptosis as vulnerable pathways in these profibrotic cells. Pharmacological targeting of pyroptosis/ferroptosis in vivo pushed cells towards adaptive repair and ameliorates fibrosis. In summary, our single-cell analysis defines key differences in adaptive and fibrotic repair and identifies druggable pathways for pharmacological intervention to prevent kidney fibrosis. After acute injury, kidneys either successfully repair/regenerate or become fibrotic. Here the authors use scRNA-seq to study adaptive/maladaptive kidney regeneration and identify proinflammatory/fibrotic proximal tubule cells with pharmacologically targetable pyroptosis/ferroptosis signatures. [ABSTRACT FROM AUTHOR]