CXC Chemokine Ligand Research Articles

Analysis of changes in the chemokine CXC ligand 13 in serum and cerebrospinal fluid of patients with neuromyelitis optica

To determine correlation between the Extended Disability Status Scale(EDSS) grade and the progression of neuromyelitis optica(NMO) patients’ levels of the chemokine CXC ligand 13 (CXCL13) in their serum and cerebrospinal fluid. This research included forty-one patients diagnosed with neuromyelitis optica(NMO) and forty-three patients diagnosed with multiple sclerosis(MS). The control group consisted of forty-three non-inflammatory neurological disease(NND) patients. The patients’ serum and cerebrospinal fluid CXCL13 levels were measured. Patients in NMO group and MS group had serum and cerebrospinal fluid with CXCL13 levels that were substantially greater than those in the NND group. When comparing the CXCL13 levels of blood and cerebrospinal fluid between patients in the EDSS ≥ 3.5 group and the EDSS<3.5 group, with the EDSS ≥ 3.5 group’s CXCL13 levels being greater(P<0.05). There was a positive correlation between the serum CXCL13 and the EDSS grades of both the NMO and MS groups(r = 0.884, P < 0.001); The cerebrospinal fluid CXCL13 of the NMO and MS groups showed a positive correlation with their EDSS grades(r = 0.681, P < 0.001). EDSS scores of NMO patients were positively correlated with their serum BLC-1 (r = 0.896, P < 0.001); EDSS scores of NMO patients were positively correlated with their cerebrospinal fluid BLC-1 (r = 0.678, P < 0.001).EDSS scores of MS patients were positively correlated with their serum BLC-1 (r = 0.852, P < 0.001); EDSS scores of MS patients were positively correlated with their cerebrospinal fluid BLC-1 (r = 0.613, P < 0.001). Serum and cerebrospinal fluid levels of CXCL13 may serve as an important biomarker for the presumptive assessment of the degree of disability in NMO and MS disease, providing a basis for the treatment and control of the disease.

A novel nomogram for predicting the morbidity of chronic atrophic gastritis based on serum CXCL5 levels

ObjectiveThis study aimed to investigate the diagnostic potential of serum CXC chemokine ligand 5 (CXCL5) in patients with chronic atrophic gastritis (CAG) and to establish a prediction model for better diagnosis of CAG.MethodsA retrospective analysis was conducted, encompassing 570 cases of CAG patients admitted to the Department of Gastroenterology of the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, who underwent gastroscopy and received pathologically confirmed diagnoses between June 2018 and June 2023. Additionally, 570 cases without CAG who underwent health checkups were included and classified into the control group. Single-factor and multi-factorial logistic regression analyses were employed to identify risk factors of CAG, and a prediction model for diagnosing CAG was developed using R software. The predictive performance of the constructed model was verified and evaluated through ROC analysis, decision curve analysis (DCA), and prediction efficacy curve.ResultsMulti-factorial logistic regression analysis revealed that history of smoking, family history of tumurs, Pepsinogen I (PG I), Gastrin 17 (G-17), Helicobacter pylori infection, D-dimer, and CXCL5 were independent risk factors in CAG patients. A nomogram for the diagnosis of CAG was constructed using R software. The ROC curve demonstrated that CXCL5 showed the best predictive efficacy as a single indicator, with an AUC of 0.897, a sensitivity of 0.789, and a specificity of 0.999. Furthermore, the nomogram exhibited an AUC of 0.992, a sensitivity of 0.958, and a specificity of 0.970. Calibration and DCA curves indicated that the predicted values of the nomogram were highly concordant with the observed values, thus demonstrating a high predictive value.ConclusionIn this study, we found a correlation between serum CXCL5 level and CAG, and developed a prediction model to assist the clinical diagnosis of CAG.

Level and clinical significance of serum CXC chemokine ligand 13 in patients with hepatocellular carcinoma

Level and clinical significance of serum CXC chemokine ligand 13 in patients with hepatocellular carcinoma

Immunoexpression of CXCL12 and CXCR4 in oral tongue squamous cell carcinoma of young and older patients.

This study analyzed the immunoexpression of C-X-C chemokine ligand 12 (CXCL12) and C-X-C chemokine receptor 4 (CXCR4) in oral tongue squamous cell carcinoma (OTSCC) of young (≤ 45 years) and older (≥ 60 years) patients and correlated the findings with clinicopathological parameters (sex, tumor size, regional metastasis, clinical stage, and histopathological grade of malignancy). Forty OTSCC cases (20 diagnosed in young patients and 20 diagnosed in older patients) were selected. Cytoplasmic (CXCL12 and CXCR4) and nuclear (CXCR4) staining percentages in epithelial and stromal cells were assessed at the invasive tumor front. Low median percentages of CXCL12 positivity were observed in epithelial and stromal cells of OTSCC in both age groups. In stromal cells, expression of this chemokine was higher in older individuals compared to young individuals (p = 0.026). Expression of CXCR4 in neoplastic cells was more frequent in older individuals, with higher median percentages of cytoplasmic (p = 0.023) and nuclear (p = 0.001) positivity compared to young individuals. In stromal cells, older individuals exhibited a significantly higher cytoplasmic expression of CXCR4 (p < 0.001). No significant differences in CXCL12 or CXCR4 immunoexpression according to clinicopathological parameters was observed in either age group (p > 0.05). Positive correlations between cytoplasmic and nuclear expressions of CXCR4 were found in young (r = 0.580; p = 0.007) and older individuals (r = 0.476;p = 0.034). The results suggest the participation of CXCR4 in the development of OTSCC, especially in older individuals. The findings also support possible age-related differences in the pathogenesis of this malignant neoplasm. Nevertheless, this protein may not be involved in the progression of OTSCC.

Curcumin targets CXCL16-mediated podocyte injury and lipid accumulation in diabetic kidney disease treatment.

Among the complications of diabetes, diabetic kidney disease (DKD) frequently emerges, typified by the detrimental effects on renal function, manifesting through inflammation, dysregulated lipid metabolism, and harm to podocytes. Existing research underscores the significance of the soluble form of C-X-C chemokine ligand 16 (CXCL16) within the context of renal impairments. However, whether CXCL16 is involved in the pathogenesis of DKD remains elusive. We report that CXCL16 levels in the serum and kidneys of individuals with DKD were elevated and correlated with various lipid parameters. The expression of CXCL16 in human podocytes subjected to high glucose or palmitic acid induction and exogenous CXCL16 administration in these cells were examined. Higher CXCL16 levels were linked to abnormal lipid metabolism. Exogenous CXCL16 administration induced lipid droplets, microfilament disorganization, apoptosis, oxidative stress, and inflammation, inhibited PPAR γ,up-regulated COX2 expression, and inhibited Nrf2 translocation in podocytes. Molecular analysis revealed that Curcumin (Cur), a polyphenolic compound derived from Curcuma longa and an Nrf2 agonist, targets the ATP-binding pocket of CXCL16, inhibiting its kinase activity. Meanwhile, Cur therapy alleviated podocyte injury, lipid accumulation, improved glomerulopathy, and reduced albuminuria. Furthermore, after silencing CXCL16 expression in podocytes using siRNA, the effects of exogenous CXCL16 were nullified, and Cur no longer exhibited any significant impact. Thus, CXCL16 participates in the pathogenesis of DKD. Inhibition of CXCL16 has shown promising results in experimental models, suggesting its beneficial effects in ameliorating DKD.

Polyphyllin VII promotes hepatic stellate cell ferroptosis via the HIC1/CX3CL1/GPX4 axis

Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of Paris polyphylla, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (HIC1), which binds to the CX3CL1 promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

Study on the changes and significance of CXCL10 level in serum of isolated polymyalgia rheumatica

ObjectiveTo investigate the significance of CXC chemokine ligand 10 (CXCL10) in the pathogenesis of isolated polymyalgia rheumatica (PMR).MethodsThe serum of six PMR patients diagnosed and treated at the First Affiliated Hospital of Wannan Medical College from September 2019 to December 2020 before treatment and after remission was collected, and the serum of six active rheumatoid arthritis (RA) patients and six healthy medical checkups were also collected, and protein microarray technology was used to detect 24 cytokines, including IL-6, IL-4, CXCL10, CXCL8, and CXCL2. Subsequently, serum was collected from other 28 patients with active PMR, 26 patients with PMR in remission, 24 patients with active RA, and 24 healthy medical checkups who were diagnosed and treated at the First Affiliated Hospital of Wannan Medical College from January 2021 to July 2023, and the enzyme-linked immunosorbent assay (ELISA) was used to validate and compare the levels of CXCL10 in each group and analyze the correlation between the levels of serum CXCL10 and the parameters of the clinical activities of PMR.ResultsProtein microarray screening revealed significant differences in CXCL10 before and after PMR treatment, and ELISA validation revealed that peripheral serum CXCL10 levels were significantly higher in the PMR-active group than in the remission group (P < 0.001), and also significantly higher than in the RA-active group (P = 0.003) and in the healthy control group (P < 0.001); correlation analysis showed a significant positive correlation between serum CXCL10 levels and serum ferritin in PMR patients (r = 0.450, P = 0.024). In the ROC curve for distinguishing PMR and RA, the area under the curve is 0.741, sensitivity = 0.643, and specificity = 0.792.ConclusionCXCL10 may play a role in the pathogenesis of isolated PMR and its level might contribute to the differential diagnosis of PMR and RA.Key Points• The concentration of CXCL10 was higher in peripheral blood of isolated PMR patients.• CXCL10 is a potential diagnostic biomarker for isolated PMR patients.• The level of CXCL10 might contribute to the differential diagnosis of PMR and RA.

Study on correlation between CXCL13 and prognosis and immune characteristics of ovarian cancer.

Ovarian cancer (OC) has a limited immunotherapeutic response; hence, this study aimed to investigate the relationship between CXC-chemokine ligand 13 (CXCL13) expression and overall survival (OS) rate, key immune pathways, degree of immune cell infiltration, and progressive disease (PD)-1 checkpoint blockade. A total of 703 differentially expressed genes were obtained from "The Cancer Genome Atlas" (TCGA) database based on the immune and stromal scores of 379 OC patients for getting the targeted gene CXCL13. The association between CXCL13 and OS in OC patients, biological function annotation of CXCL13, and its correlation with immune components were assessed. The results indicated that upregulated CXCL13 expression was positively correlated with better OC patient prognosis. CXCL13 expression was associated with 6 immune-related pathways, 10 immune cells, and PD-1 expression of OC micro-environment. Moreover, high expression of CXCL13 was related to a better tumor response and more extended tumor-stable stage after PD-1 blocking therapy in IMvigor210. The study concluded that CXCL13 could be a prognostic marker and a potential immunotherapy target for OC patients, especially PD-1 checkpoint blockade.

Intrauterine adhesions repair with menstrual blood-derived mesenchymal stem cells via CXCL13-CXCR5 signal axis and its mechanism

BackgroudIntrauterine Adhesions (IUA) is a common gynecological disease which is seriously endangers the reproductive function of women without any ideal treatment. Some researchers found Menstrual Blood-derived Mesenchymal Stem Cells (MenSCs) can repair of damaged endometrium, however, has not been fully clarified. This study aims to evaluate the therapeutic effects of MenSCs in IUA and the repair mechanism in vivo.MethodsThis study is Laboratory-based study. To evaluate the therapeutic effects of MenSCs in IUA, We cultivated MenSCs, established mouse endometrial injury model, observed the uterine morphology and degree of endometrial fibrosis and compared the expression of CXC chemokine ligand-13 (CXCL13)、CXC chemokine receptor-5 (CXCR5)、Plasmin Activating Inhibitor-1(Pai-1), Transforming Growth Faction-β1(TGF- β1) and Matrix Metalloproteinase-9 (Mmp-9) among each groups. GraphPad Prism 8.0 was used for statistical processing. Data were expressed as mean ± SD. Statistical comparisons among groups were performed with one-way ANOVA. P < 0.05 were considered statistically significant.ResultsWe successfully cultured and identified MenSCs and established mice model of uterine adhesion. After treatment with MenSCs, endometrial morphology of mice was partially restored, endometrial thickness was increased, and glands were multipiled. The concentrations of CXCL13 and CXCR5 were significantly increased by immunofluorescence detection compared with the control group. The results of RT-qPCR showed that the expressions of Pai-1 and Mmp-9 were significantly lower than those of the control group.ConclusionsMenSCs may reduce endometrial fibrosis and the down-regulating expression of Pai-1、Mmp-9 and CXCL13-CXCR5 axis were involved in the process of MenSCs repaired IUA.

Bone Destruction-Chemotactic Osteoprogenitor Cells Deliver Liposome Nanomedicines for the Treatment of Osteosarcoma and Osteoporosis.

Therapeutic efficacy of skeletal diseases is usually limited by unfavorable drug delivery due to incapable bone targeting and low bone affinity of conventional drug carriers, as well as relatively reduced vascularization and dense structure of bone tissues. Due to CXC chemokine receptor 4 (CXCR4)/CXC chemokine ligand 12 (CXCL12) signal axis-guided recruitment, osteoprogenitor cells (OPCs) can actively migrate to bone disease nidus. Here, drugs-loaded nanoliposomes are prepared and decorated onto OPCs by biotin-streptavidin linkage for precise bone disease targeting and effective drug delivery. In mouse models of tibia defect and orthotopic osteosarcoma, superior targeting property of OPCs-based drug delivery systems toward diseased bone niduses is verified. By encapsulating antitumor and antiosteoporosis drugs into nanoliposomes, OPCs-based drug delivery systems effectively inhibit disease development and restore bone destruction in mouse models of orthotopic osteosarcoma and ovariectomized osteoporosis. This study reveals a cell-based drug delivery system for precise bone disease targeting and highly effective drug delivery, which will find great potential as a universal drug delivery platform for targeting treatment of various bone diseases.

Differential expression and significance of cytokines in cerebrospinal fluid of patients with viral encephalitis

To extensively identify cerebrospinal fluid (CSF) cytokine profiles related to the occurrence, development and prognosis of viral encephalitis (VE) patients by using a high-throughput proteomic approach.We measured 80 cytokines in the CSF of acute-phase VE patients (n = 11) using high-throughput protein chip technology, comparing them to controls (n = 6). ELISA validated these findings and assessed additional cytokines from prior literature in a larger cohort (15 VE patients, 15 controls). Correlations between biomarkers and clinical characteristics were also examined.In the initial stage, we identified two differentially expressed cytokines: cathepsin-L (CTSL), which was up-regulated, and Fractalkine, which was down-regulated. Functional enrichment analysis revealed that these proteins are linked to inflammation, apoptosis, autophagy, and blood-brain barrier disruption. In stage2, the elevations of cathepsin-L (CTSL), fractalkine, interleukin-6 (IL-6), IL-1β, macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α), insulin-like growth factor Ⅱ (IGF-2) and CXC chemokine ligand 10 (CXCL10) in VE were validated by ELISA. The results of linear regression indicated that these cytokines was positively correlated with CSF reactive lesions (p < 0.05).In this study, some biomarkers related with CSF level changes and prognosis were obtained. Although these cytokines are not specific, they may be related to the occurrence and development of VE. CTSL, MIF, IL-1β, TNF-α and CXCL10 can be used as VE potential biomarkers. These cytokines may participate in the pathogenesis of VE through inflammatory response, cell apoptosis, autophagy, blood-brain barrier disruption and cytokine-cytokine receptor interaction pathway.

Effect of interleukin-17A on inflammatory mediator production in interleukin-1β-stimulated human dental pulp fibroblasts.

In response to pro-inflammatory cytokines such as interleukin (IL)-1β, dental pulp fibroblasts produce various inflammatory mediators, including IL-6, IL-8, CC chemokine ligand 20 (CCL20), and CXC chemokine ligand 10 (CXCL10), leading to the progression of pulpitis. IL-17/IL-17A (IL-17A) is a pro-inflammatory cytokine secreted by T helper (Th) 17 cells following their recruitment to inflamed sites; however, the roles of IL-17A during pulpitis remain unclear. The purpose of this study was to investigate the effect of IL-17A on IL-6, IL-8, CCL20 and CXCL10 production by human dental pulp fibroblasts (HDPFs) in vitro. IL-17A at a concentration of 100ng/ml induced the production of 10 times more IL-8 and 4 times more CXCL10, but not IL-6 and CCL20, compared to controls. Co-stimulation of HDPFs with IL-17A and IL-1β synergistically enhanced the production of IL-6, CCL20, IL-8 and CXCL10. IL-1β increased expression of IL-17 receptor/IL-17RA (IL-17R) on HDPFs. Moreover, the cell signal pathways of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were more potently activated by simultaneous stimulation with IL-17A and IL-1β. These findings suggest that IL-17A participates in the progression of dental pulp inflammation through the enhanced production of inflammatory mediators in HDPFs.

Open-Source Throttling of CD8+ T Cells in Brain with Low-Intensity Focused Ultrasound-Guided Sequential Delivery of CXCL10, IL-2, and aPD-L1 for Glioblastoma Immunotherapy.

Improving clinical immunotherapy for glioblastoma (GBM) relies on addressing the immunosuppressive tumor microenvironment (TME). Enhancing CD8+ T cell infiltration and preventing its exhaustion holds promise for effective GBM immunotherapy. Here, a low-intensity focused ultrasound (LIFU)-guided sequential delivery strategy is developed to enhance CD8+ T cells infiltration and activity in the GBM region. The sequential delivery of CXC chemokine ligand 10 (CXCL10) to recruit CD8+ T cells and interleukin-2 (IL-2) to reduce their exhaustion is termed an "open-source throttling" strategy. Consequently, up to 3.39-fold of CD8+ T cells are observed with LIFU-guided sequential delivery of CXCL10, IL-2, and anti-programmed cell death 1 ligand 1 (aPD-L1), compared to the free aPD-L1 group. The immune checkpoint inhibitors (ICIs) therapeutic efficacy is substantially enhanced by the reversed immunosuppressive TME due to the expansion of CD8+ T cells, resulting in the elimination of tumor, prolonged survival time, and long-term immune memory establishment in orthotopic GBM mice. Overall, LIFU-guided sequential cytokine and ICIs delivery offers an "open-source throttling" strategy of CD8+ T cells, which may present a promising strategy for brain-tumor immunotherapy.

Cardamonin inhibits the expression of inflammatory mediators in TNF-α-stimulated human periodontal ligament cells

Objective Periodontis is a chronic inflammatory disease induced by periodontopathogenic bacteria. The excessive immune response caused by persistent bacterial infection leads to alveolar bone resorption and ultimately tooth loss. Cardamonin is a biologically active substance that is found in the Zingiberaceae family, such as Alpinia zerumbet, and is classified as a natural chalcone. There have been no attempts to use cardamonin for the treatment of periodontitis, and no reports have examined the effects of cardamonin on periodontal tissue component cells. The aim of this study was to analyze effects of cardamonin on expression of inflammation mediators produced by TNFα-stimulated human periodontal ligament cells (HPDLCs), including its effects on signal transduction molecules. Methods Cytokine and chemokine levels were measured by ELISA. Protein expression in HPDLCs and activations of signal transduction pathway were determined by Western blotting. Results Our results indicate that cardamonin suppresses C-C motif chemokine ligand (CCL)2, CCL20, C-X-C motif chemokine ligand (CXCL)10, and interleukin (IL)-6 production and intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 expression in TNF-α-stimulated HPDLCs. In addition, cardamonin induced the expression of the antioxidant enzyme, Heme Oxygenase (HO)-1, in HPDLCs. Furthermore, cardamonin suppressed TNF-α-stimulated c-Jun N-terminal kinase (JNK), nuclear factor (NF)-κB, and signal transducer and activator of transcription (STAT)3 signaling pathways in HPDLCs. Conclusion We show that cardamonin reduces inflammatory mediator production by inhibiting the activation of several signaling pathways in this manuscript.

Blood metabolites mediate the causal relationship between circulating CX3CL1 levels and prostate cancer: A 2-step Mendelian randomization study.

Chemokines influence the progression of prostate cancer (PCa) through multiple mechanisms. However, the effect of C-X3-C chemokine ligand 1 (CX3CL1) on PCa risk remains controversial. Our study aimed to investigate whether circulating CX3CL1 is causally associated with PCa and to identify metabolites that have mediating effects using the 2-step bidirectional Mendelian randomization (MR) analysis process. Inverse variance weighting (IVW) results were used as the primary observations, while additional sensitivity analyses were conducted. For each standard deviation increase exhibited by the circulating CX3CL1 levels, the risk of PCa was reduced by 0.4% (IVW: OR = 0.996, [95% CI = 0.994-0.998], P < .001), and blood alliin levels increased by 19% (IVW: OR = 1.185, [95% CI = 1.01-1.54], P = .003). For each standard deviation increase in the blood alliin levels, the risk of PCa was reduced by 0.1% (IVW: OR = 0.999, [95% CI = 0.997-0.999], P = .03). Therefore, the protective effect of circulating CX3CL1 on PCa may be mediated by blood alliin levels (mediated proportion = 6.7%). The results supported the notion that high levels of circulating CX3CL1 indicate a lower PCa risk and the idea that the food-derived antioxidant alliin may mediate this association. We emphasize that the use of CX3CL1 as a protective factor against PCa may provide new strategies for PCa prevention and care in the future.

Anti-inflammatory effect and its mechanism of Saracae Cortex based on zebrafish model and network pharmacology

This paper aims to explore the anti-inflammatory mechanism of Saracae Cortex by using network pharmacology and molecular docking methods and verify it through the inflammation model of zebrafish. The effective components, potential core targets, and signaling pathways of Saracae Cortex were obtained by using network pharmacology. A lipopolysaccharide(LPS)-induced inflammation model of zebrafish was established to evaluate the anti-inflammatory activity of aqueous extract and 70% ethanol extract of Saracae Cortex with cell apoptosis rate and reactive oxygen species(ROS) production rate as indicators. q PCR was performed to verify the main targets predicted by network pharmacology. The prediction found that there were 121 potential anti-inflammatory targets in Saracae Cortex. Protein-protein interaction(PPI) analysis showed that Saracae Cortex mainly acted on signal transducer and activator of transcription 3(STAT3), vascular endothelial growth factor A( VEGFA), epidermal growth factor( EGF), tumor necrosis factor( TNF),tumor protein p53(TP53), matrix metalloprotein 9(MMP9), c-fos proto-oncogene protein(FOS), estrogen receptor 1(ESR1), cx-c motif chemokine ligand 8(CXCL8), cluster of differentiation 8(CD8), and other targets. Gene Ontology(GO) analysis showed the biological process mainly acted on the inhibition of apoptosis, the positive regulation of gene expression, and the positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that the mitogen-activated protein kinase(MAPK) signaling pathway, PI3K-Akt signaling pathway, and hypoxia-inducible factor 1(HIF-1) signaling pathway may play a key role in anti-inflammation of Saracae Cortex. Molecular docking verified that five key compounds had a strong binding force with their corresponding core target. Zebrafish animal experiments showed that Saracae Cortex could significantly inhibit ROS formation and reduce cell apoptosis in juvenile fish caused by inflammation and inhibit the further enhancement of inflammatory response in tissue. In addition, compared with the blank group, the transcription levels of nuclear factor kappa-B(NF-κB), TP53, FOS, adaptor protein complex-1(AP-1), and mitogen-activated protein kinases P38(P38) were significantly up-regulated in the model group. Compared with the model group, the m RNA expression of NF-κB, TP53, FOS, AP-1, and P38 was significantly down-regulated in zebrafish tissue treated with aqueous extract and 70% ethanol extract of Saracae Cortex. Saracae Cortex plays an anti-inflammatory role through multiple components and targets, and its anti-inflammatory effect may be related to the inhibition of the MAPK signaling pathway.

Acupuncture alleviates inflammatory pain by activating CXCL1/CXCR2 signaling in the primary somatosensory cortex in adjuvant induced arthritis rats.

To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.

Deciphering microglial activation and neuronal apoptosis post‑traumatic brain injury: The role of TYROBP in inflammation regulation networks.

Traumatic Brain Injury (TBI) represents a significant public health challenge. Recovery from brain injury necessitates the collaborative efforts of various resident neural cells, predominantly microglia. The present study analyzed rat and mouse RNA expression micro‑arrays, high‑throughput RNA sequencing and single‑cell sequencing data sourced from public databases. To construct an inflammation regulation network around TYRO protein tyrosine kinase‑binding protein (TYROBP), to evaluate the role of TYROBP in cell death after TBI. These findings indicate that following TBI, neurons predominantly communicate with one another through the CXC chemokine ligand (CXCL) and CC chemokine ligand (CCL) signaling pathways, employing a paracrine mechanism to activate microglia. These activated microglia intensify the pathological progression of brain injury by releasing factors such as tumor necrosis factor α (TNF‑α), vascular endothelial growth factor and transforming growth factor β via the NF‑κB pathway. Cells co‑culture experiments demonstrated that neurons, impaired by mechanical injury, interact with microglia through non‑contact mechanisms. Activated microglia secrete cytokines, including TNF‑α, CXCL‑8 and CCL2, which trigger an inflammatory response and facilitate neuronal apoptosis. TYROBP gene knockout in microglia was demonstrated to reduce this interaction and reduce neuronal cell apoptosis rates.

Activation of RIG-I signaling in the early stage of Paragonimus proliferus infection causes lung injury via type I immune response in rat.

Paragonimiasis is a common zoonotic parasitic disease. The retinoic acid-inducible gene I (RIG-I) signaling is very important for the host to recognize invading pathogens (especially viruses and bacteria). However, the role of RIG-I signaling in the early stages of P. proliferus infection remains unclear. Therefore, in this study, Sprague-Dawley (SD) rat models with lung damage caused by P. proliferus were established. Experimental methods including Enzyme-linked Immuno Sorbent Assay (ELISA), real-time fluorescent quantitative polymerase chain reaction (PCR), western blotting, and hematoxylin and eosin (HE) staining were used to explore the mechanisms of lung injury caused by P. proliferus. As a result, the expression of the mRNA and proteins of RIG-I signal-related key target molecules, including RIG-I, tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), interferon regulatory Factor 7 (IRF7), IPS-1, and downstream C-X-C chemokine ligand 10 (CXCL10), were significantly up-regulated immediately after infection, peaked at 3 or 7 days, and showed a downward trend on after 14 days. The levels of pro-inflammatory cytokines interleukin-1 (IL-1), interferon (IFN)-α, -β, and -γ, which represent type 1 immune response, gradually increased and reached a peak by 14 days, which was consistent with the changes in the degree of inflammatory damage observed under HE staining of lung tissues. In conclusion, RIG-I signaling is activated in the early stage (before 14 days) of P. proliferus infection, it is inferred that the lung injury of the host may be related to the activation of RIG-I like signaling to induce type I immune response.

Inflammatory responses in esophageal mucosa before and after laparoscopic antireflux surgery.

Currently, the primary treatment for gastroesophageal reflux is acid suppression with proton pump inhibitors, but they are not a cure, and some patients don't respond well or refuse long-term use. Therefore, alternative therapies are needed to understand the disease and develop better treatments. Laparoscopic anti-reflux surgery (LARS) can resolve symptoms of these patients and plays a significant role in evaluating esophageal healing after preventing harmful effects. Successful LARS improves typical gastroesophageal reflux symptoms in most patients, mainly by reducing the exposure time to gastric contents in the esophagus. Amelioration of the inflammatory response and a recovery response in the esophageal epithelium is expected following the cessation of the noxious attack. To explore the role of inflammatory biomolecules in LARS and assess the time required for esophageal epithelial recovery. Of 22 patients with LARS (pre- and post/5.8 ± 3.8 months after LARS) and 25 healthy controls (HCs) were included. All subjects underwent 24-h multichannel intraluminal impedance-pH monitoring and upper gastrointestinal endoscopy, during which esophageal biopsy samples were collected using endoscopic techniques. Inflammatory molecules in esophageal biopsies were investigated by reverse transcription-polymerase chain reaction and multiplex-enzyme-linked immunosorbent assay. Post-LARS samples showed significant increases in proinflammatory cytokines [interleukin (IL)-1β, interferon-γ, C-X-C chemokine ligand 2 (CXCL2)], anti-inflammatory cytokines [CC chemokine ligand (CCL) 11, CCL13, CCL17, CCL26, CCL1, CCL7, CCL8, CCL24, IL-4, IL-10], and homeostatic cytokines (CCL27, CCL20, CCL19, CCL23, CCL25, CXCL12, migration inhibitory factor) compared to both HCs and pre-LARS samples. CCL17 and CCL21 levels were higher in pre-LARS than in HCs (P < 0.05). The mRNA expression levels of AKT1, fibroblast growth factor 2, HRAS, and mitogen-activated protein kinase 4 were significantly decreased post-LARS vs pre-LARS. CCL2 and epidermal growth factor gene levels were significantly increased in the pre-LARS compared to the HCs (P < 0.05). The presence of proinflammatory proteins post-LARS suggests ongoing inflammation in the epithelium. Elevated homeostatic cytokine levels indicate cell balance is maintained for about 6 months after LARS. The anti-inflammatory response post-LARS shows suppression of inflammatory damage and ongoing postoperative recovery.