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Electrical signaling plays a crucial role in the cellular response to tissue injury in wound healing and an external electric field (EF) may expedite the healing process. Here, we have developed a standalone, wearable, and programmable electronic device to administer a well-controlled exogenous EF, aiming to accelerate wound healing in an in vivo mouse model to provide pre-clinical evidence. We monitored the healing process by assessing the re-epithelization rate and the ratio of M1/M2 macrophage phenotypes through histology staining. Following three days of treatment, the M1/M2 macrophage ratio decreased by 30.6% and the re-epithelization in the EF-treated wounds trended towards a non-statically significant 24.2% increase compared to the control. These findings provide point towards the effectiveness of the device in shortening the inflammatory phase by promoting reparative macrophages over inflammatory macrophages, and in speeding up re-epithelialization. Our wearable device supports the rationale for the application of programmed EFs for wound management in vivo and provides an exciting basis for further development of our technology based on the modulation of macrophages and inflammation to better wound healing., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hernandez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Neutrophils are the most abundant leukocytes and usually the first immune cell-type recruited to a site of infection or tissue damage. In asphyxiated neonates, elevated peripheral neutrophil counts are associated with poorer neurological outcomes. Induced neutropenia provides brain protection in animal models of neonatal hypoxic-ischemic (HI) injury, but the anti-neutrophil serum used in past studies heavily cross-reacts with monocytes, thus complicating the interpretation of results. Here we examined neutrophil influx and extravasation, and used a specific anti-Ly6G antibody for induced neutropenia against lipopolysaccharide (LPS)-pretreated HI injury in murine neonates, a model for inflammation-sensitized hypoxic-ischemic encephalopathy (HIE). As early as 6 h after the LPS/HI insult, the mRNAs for neutrophil-recruiting and mitogenic chemokines ascended in the ipsilateral hemisphere, coinciding with immuno-detection of neutrophils. However, neutrophils mainly resided within blood vessels, exhibiting signs for neutrophil extracellular traps (NETs), before 48 h post-LPS/HI. Prophylactic anti-Ly6G treatment blocked the brain infiltration of neutrophils, but not monocytes or lymphocytes, and markedly decreased LPS/HI-induced pro-inflammatory cytokines, matrix metalloproteinase 9 (MMP-9), and brain tissue loss. In contrast, anti-Ly6G treatment at 4 h post-LPS/HI failed to prevent the influx of neutrophils and brain damage. Together, these results suggest important pathological functions for early-arriving neutrophils in inflammation-sensitized HIE.

Fibrinogen is a protein that reflects systemic inflammation and regulates the immune response to disease. However, there is a scarcity of data on fibrinogen in recurrent aphthous stomatitis (RAS). We aimed to test the hypothesis that fibrinogen is involved in the aetiology of RAS. Between November 2016 and November 2018, we included 109 minor RAS patients and 29 age‐ and sex‐matched controls in a single‐center, observational study. Their clinical history and ulcer manifestations led to the diagnosis of minor RAS. The ulcer severity score (USS) was used to assess disease severity, and fibrinogen was also collected. We conducted three analyses: Analysis 1 (comparison of fibrinogen levels between patients and controls), Analysis 2 (comparison of fibrinogen levels between high and low USS patients) and Analysis 3 (comparison of fibrinogen levels between before and after anti‐inflammatory treatment in patients). The fibrinogen levels in the 109 minor RAS patients were statistically higher than in the 29 controls (mean [SD], 2.6 [0.5] vs. 2.3 [0.3]; Student's t‐test, p < 0.001). However, there were no significant differences in fibrinogen levels among the 43 patients with high USS and the 39 patients with low USS (mean [SD], 2.7 [0.5] vs. 2.6 [0.4]; Student's t‐test, p = 0.278). Furthermore, fibrinogen levels were significantly higher before anti‐inflammatory treatment in comparison to those after anti‐inflammatory treatment in the 35 paired patients (mean [SD], 2.6 [0.4] vs. 2.5 [0.4]; Student's t‐test, p = 0.026). Interestingly, fibrinogen levels were significantly higher in the 35 paired patients after anti‐inflammatory treatment compared to the 29 control subjects (mean [SD], 2.5 [0.4] vs. 2.3 [0.3]; Student's t‐test, p = 0.026]. Fibrinogen may play a role in the aetiology of RAS and may be a drug target for RAS treatment. Clinicians should be alert that high serum fibrinogen levels might be associated with the risk of RAS. [ABSTRACT FROM AUTHOR]

Ethanol, also known as alcohol, is one of the most common drinks in the world. Chronic ethanol exposure has been reported to induce mental disorders. Ethanol also has a strong effect on the gut microbiota. The gut microbiota has been reported to affect the brain via multiple pathways, including changes in γ-aminobutyric acid (GABA) system, and cause a variety of mental disorders. The GABA system in the cortex is associated with anxiety. However, the role of gut microbiota played in ethanol exposure-induced changes in the GABA system and anxiety is still not clear. We established a 30-day ethanol exposure mouse model and investigated the effects of microbiota using the antibiotic minocycline. Minocycline alleviated ethanol-induced anxiety-like behaviour, dysbiosis of microbiota, intestinal barrier disruption, increased serum endotoxin and interleukin (IL)-6. Minocycline also attenuated ethanol-induced apoptosis and decreased expression of glutamate decarboxylases (GADs) and GABRA1 in the prefrontal cortex. Our results indicated that gut microbiota plays an important role in ethanol-induced anxiety-like behaviour by altering the function of GABA system. In addition, causal mediation analysis showed that endotoxin and IL-6 may mediate the connection between the gut microbiota and the expression of GABAA receptor in the prefrontal cortex. [ABSTRACT FROM AUTHOR]

Purpose: Our research developed immune-related long noncoding RNAs (lncRNAs) for risk stratification in cervical cancer (CC) and explored factors of prognosis, inflammatory microenvironment infiltrates, and chemotherapeutic therapies. Methods: The RNA-seq data and clinical information of CC were collected from the TCGA TARGET GTEx database and the TCGA database. lncRNAs and immune-related signatures were obtained from the GENCODE database and the ImPort database, respectively. We screened out immune-related lncRNA signatures through univariate Cox, LASSO, and multivariate Cox regression methods. We established an immune-related risk model of hub immune-related lncRNAs to evaluate whether the risk score was an independent prognostic predictor. The xCell and CIBERSORTx algorithms were employed to appraise the value of risk scores which are in competition with tumor-infiltrating immune cell abundances. The estimation of tumor immunotherapy response through the TIDE algorithm and prediction of innovative recommended medications on the target to immune-related risk model were also performed on the basis of the IC50 predictor. Results: We successfully established six immune-related lncRNAs (AC006126.4, EGFR-AS1, RP4-647J21.1, LINC00925, EMX2OS, and BZRAP1-AS1) to carry out prognostic prediction of CC. The immune-related risk model was constructed in which we observed that high-risk groups were strongly linked with poor survival outcomes. Risk scores varied with clinicopathological parameters and the tumor stage and were an independent hazard factor that affect prognosis of CC. The xCell algorithm revealed that hub immune-related signatures were relevant to immune cells, especially mast cells, DCs, megakaryocytes, memory B cells, NK cells, and Th1 cells. The CIBERSORTx algorithm revealed an inflammatory microenvironment where naive B cells (p < 0.01), activated dendritic cells (p < 0.05), activated mast cells (p < 0.0001), CD8+ T cells (p < 0.001), and regulatory T cells (p < 0.01) were significantly lower in the high-risk group, while macrophages M0 (p < 0.001), macrophages M2 (p < 0.05), resting mast cells (p < 0.0001), and neutrophils (p < 0.01) were highly conferred. The result of TIDE indicated that the number of immunotherapy responders in the low-risk group (124/137) increased significantly (p = 0.00000022) compared to the high-risk group (94/137), suggesting that the immunotherapy response of CC patients was completely negatively correlated with the risk scores. Last, we compared differential IC50 predictive values in high- and low-risk groups, and 12 compounds were identified as future treatments for CC patients. Conclusion: In this study, six immune-related lncRNAs were suggested to predict the outcome of CC, which is beneficial to the formulation of immunotherapy. [ABSTRACT FROM AUTHOR]

Renal inflammation can result in renal injury. Uric acid (UA) is the final product of purine metabolism in humans and because of the lack of urate oxidase, UA may accumulate in tissues, including kidney, causing inflammation. Galangin was isolated from a traditional Chinese medicine plant and possesses several beneficial effects, working as an anti-oxidant, anti-mutagenic, anti-tumor, anti-inflammatory, anti-microbial, and anti-viral agent. Therefore, this study aimed at investigating the molecular mechanism of galangin in the attenuation of UA induced renal inflammation in normal rat kidney epithelial cells NRK-52E. Our findings suggested that galangin treatment efficiently protected NRK-52E cells against UA induced renal inflammation by decreasing tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-18, prostaglandin E2 (PGE2), and nitric oxide (NO) release, and it inhibited nitric oxide synthase (iNOS), prostaglandin endoperoxide synthase 2 (PTGS2), TNF-α, IL-1β, and IL-18 mRNA expression. In addition, galangin was not exerting any cytotoxicity at the concentrations that were effective against inflammation as assessed by CCK8 assay. Moreover, western blotting showed that galangin treatment effectively inhibited nuclear factor-kappa B (NF-κB), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) and nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3) signaling pathway activation. Taken together, these findings suggested that galangin plays a pivotal role in renal inflammation by suppressing inflammatory responses, which might be closely associated with the inhibition of NLRP3 inflammasome, NF-κB and PI3K/AKT signaling pathway activation. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the protective effect of chicoric acid on oxidative stress and inflammation in rats with cerebral ischemia-reperfusion injury. A cerebral ischemia-reperfusion injury rat model was created via transient middle cerebral artery occlusion (MCAO) and rats were treated with various doses of chicoric acid (0, 1, 10 and 100 mg/kg). Neurological deficits and infarct volume were used to estimate the protective effects of chicoric acid treatment. Levels of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, nitric oxide (NO) and prostaglandin E2 (PGE2) were assessed. Western blot analysis was also used to measure the expression of cyclooxygenase (COX)-2, p38-mitogen activated protein kinase (MAPK), c-Jun, phosphorylated protein kinase B (p-AKT) and AKT. Chicoric acid exposure was observed to reduce neurological deficits and infarct volume in rats with cerebral ischemia-reperfusion injury. In addition, ROS production and inflammation were significantly suppressed following treatment with chicoric acid. Chicoric acid was demonstrated to significantly inhibit the upregulation of NO and PGE2 levels in rats following MCAO. Furthermore, chicoric acid significantly suppressed the MCAO-induced promotion of COX-2, p38-MAPK and c-Jun protein expression and enhanced the inhibition of p-AKT/AKT. These results suggest that chicoric acid has a protective effect, preventing oxidative stress and inflammation in rats with cerebral ischemia-reperfusion injury via the p38-MAPK, c-Jun and AKT signaling pathways. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the antimalarial activity of synthetic hepcidin and its effect on cytokine secretion in mice infected with Plasmodium berghei . The mice were infected with P. berghei intravenously and treated with hepcidin according to 4-day suppression test and Rane's test. The serum levels of interleukins (IL-1 β , IL-2, IL-6, IL-10, IL-12p70, and IL-17A), tumor necrosis factor- α (TNF- α ), and interferon- γ (IFN- γ ) in the experimental mice were determined using a cytometric bead array (CBA) kit. The survival rate of the infected mice was also registered. Additionally, the serum iron, alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (BIL) were detected to evaluate liver functions. Hepcidin exerted direct anti-malarial function in vivo and increased survival rate in a dose-dependent manner. In addition, the secretion of T helper cell type 1 (Th1), Th2, and Th17 cytokines, TNF- α, and IFN- γ were inhibited by hepcidin. In conclusion, our results demonstrated that synthetic hepcidin exerts in vivo antimalarial activity and possesses anti-inflammatory function, which provides a basis for future design of new derivatives with ideal anti-malarial activity. [ABSTRACT FROM AUTHOR]

• Macrophages in the gut originate from the embryo and the circulation. • Gut macrophages can be anatomically classified into mucosal and muscularis subsets. • Macrophages function as multitaskers in the gut inflammation and fibrosis. • Anti-fibrotic macrophages regulate the regression of gut fibrosis. Intestinal macrophages are heterogenous cell populations with different developmental ontogeny and tissue anatomy. The concerted actions of intestinal macrophage subsets are critical to maintaining tissue homeostasis. However, the dysregulation of macrophages following tissue injury or chronic inflammation could also lead to intestinal fibrosis, with few treatment options in the clinic. In this review, we will characterize the features of intestinal macrophages in light of the latest advances in lineage tracing and single-cell sequencing technology. The roles of macrophages in distinct stages of intestinal fibrosis would be also elaborated. Finally, based on the reciprocal interaction between macrophages and intestinal fibrosis, we will propose the potential macrophage targeting anti-intestinal fibrosis therapies. [ABSTRACT FROM AUTHOR]

Objectives To review the literature and provide an update on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions. Methods We performed PubMed database searches through June 2014 for relevant studies in the English literature published since the last update of colchicine in 2008. Searches encompassed colchicine mechanisms of action and clinical applications in medical conditions. A total of 381 articles were reviewed. Results The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, inhibition of pore formation activated by purinergic receptors P2X7 and P2X2, and stimulation of dendritic cell maturation and antigen presentation. Colchicine also has anti-fibrotic activities and various effects on endothelial function. The therapeutic use of colchicine has extended beyond gouty arthritis and familial Mediterranean fever, to osteoarthritis, pericarditis, and atherosclerosis. Conclusion Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions. [ABSTRACT FROM AUTHOR]

• LV function was improved after iCS-IL37 transplantation. • Infarct size was decreased after iCS-IL37 transplantation. • Pro-inflammatory cytokines were down-regulated by iCS-IL37. Myocardial ischemia-reperfusion injury (MI-RI) has many adverse complications with high mortality rate. In the current study, we investigated the therapeutic advantages of delivering Interleukin-37 (IL-37) by induced cardiospheres (iCS), generated from adult skin fibroblasts via somatic reprogramming, in treating the mice model MI-RI. The mouse model of MI-RI was established and the iCS cells with IL-37 overexpression (iCS-IL37) were transplanted into the mice via tail-vein injection. Left ventricular (LV) dimensions and LV pressure-volume measurements were assessed by parasternal long-axis echocardiography and hemodynamic assessment. The infarct size was determined by histology analysis. And the inflammatory responses were analyzed by using enzyme-linked immunosorbent assay (ELISA). The LV function was significantly improved after the iCS-IL37 transplantation when compared to the vehicle control group and iCS group, including the end-systolic pressure and dP/dtMax. Furthermore, the infarct size was significantly decreased after the iCS-IL37 transplantation. The protein levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were down-regulated by the iCS-IL37 transplantation. The present study indicated that the iCS with IL-37 overexpression had therapeutic effects on the mice model of MI-RI. [ABSTRACT FROM AUTHOR]

• Chronic ethanol exposure could induce anxiety-like behavior in male C57BL/6 mice. • Chronic ethanol exposure could induce neuroinflammation in male C57BL/6 mice. • Ethanol could induce neuroinflammation through the TLR3/NF-κB pathway. Chronic alcoholism has become a major public health problem. Long-term and excessive drinking can lead to a variety of diseases. Chronic ethanol exposure can induce neuroinflammation and anxiety-like behavior, and this may be induced through the Toll-like receptor 3/nuclear factor-κB (TLR3/NF-κB) pathway. Animal experiments were performed using healthy adult male C57BL/6 N mice given 10 % (m/V) or 20 % ethanol solution as the only choice of drinkable fluid for 60, 90 or 180 d. In cell culture experiments, H4 human glioma cells were treated with 100 mM ethanol for 2 d, with the TLR3 gene silenced by RNAi and NF-κB inhibited by ammonium pyrrolidine dithiocarbamate (PDTC, 10 μM). After treatment with ethanol solution for a specific time, the anxiety-like behavior of the mice was tested using the open field test and the elevated plus maze test. Western blotting was used to detect the expression of TLR3, TLR4, NF-κB, IL-1β, IL-6, and TNF-α in the mouse hippocampus and H4 cells. The expression of IL-1β, IL-6 and TNF-α in the supernatant of cell culture medium was detected by ELISA. The open field test showed a decrease in time spent in the central area, and the elevated plus maze test showed a decrease in activity time in the open arm region. These behavioral tests indicated that ethanol caused anxiety-like behavior in mice. The expression levels of TLR3, TLR4, NF-κB, IL-1β, IL-6, and TNF-α increased after ethanol exposure in both the hippocampus of mice and H4 cells. Silencing of the TLR3 gene by RNAi or inhibition of NF-κB by PDTC attenuated the ethanol-induced increase in the expression of inflammatory factors in H4 cells. These findings indicated that chronic ethanol exposure increases the expression of TLR3 and NF-κB and produces neuroinflammation and anxiety-like behavior in male C57BL/6 mice and that ethanol-induced neuroinflammation can be caused through the TLR3/NF-κB pathway. [ABSTRACT FROM AUTHOR]