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Background/Objectives: Chronic Limb-Threatening Ischemia (CLTI) is a chronic limb ischemic disease caused by vascular lesions, characterized by pain, ulcers, and gangrene, which can be life-threatening in severe cases. The objective of this study is to explore whether Berbamine (BBM) can protect against and repair ischemic muscle tissue in the lower limbs; Methods: Using a mouse hindlimb ischemia (HLI) model, 36 C57BL6 mice were divided into sham, HLI, and HLI+BBM treatment groups. Results: Our findings indicate that BBM can restore motor function and muscle tissue pathology in mice, potentially by inhibiting the nuclear translocation of nuclear factor kappa-B (NF-κB), thereby alleviating tissue inflammation caused by chronic ischemia, reducing muscle cell apoptosis, inhibiting M1 macrophage polarization, and promoting angiogenesis. Conclusions: Our research suggests that BBM has the potential to protect against ischemic damage in lower limb muscle tissue, providing a new approach to the treatment of CLTI. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effect of skullcapflavone II (SCF-II) on the epithelial-mesenchymal transition (EMT) induced by transforming growth factor beta (TGF-β) in human corneal epithelial cells (HCECs), as well as to identify the signaling pathways that may be involved. METHODS: HCECs were cultured in vitro. At a SCF-II (5, 10 µmol/L) dose, cell viability was analysed with a cell counting kit-8 (CCK-8) assay, and cell migration was monitored with wound healing and Transwell migration assays. There were 4 groups: SCF-II, TGF-β, SCF-II+TGF-β and Control. Western blotting and immunofluorescence were performed to show the expression of EMT markers and the translocation of nuclear factor kappa-B (NF-κB) into the nucleus in the 4 groups. RESULTS: Treatment with SCF-II decreased HCEC viability in a dose-dependent manner. A concentration below 10 µmol/L did not present obvious cell toxicity, and survival rates were more than 70% at 48h. Treatment with SCF-II (5 and 10 µmol/L) significantly impeded migration in wound healing and Transwell migration assays (P

Objective To investigate the effect of resveratrol (RSV) in the treatment of peri-implantitis in a murine model and its effect on nuclear factor kappa-B (NF-κB) signaling and mitogen-activated protein kinase (MAPKs) signaling. Methods This study has been reviewed and approved by the Ethics. After extracting the right maxillary molars of 40 C57BL/6 mice and allowing them to heal naturally for 8 weeks, implants were implanted at the site of the first molar. The mice were randomly divided into a control group, a mouse peri implantitis model group, a low-dose group of 20 mg/kg resveratrol (RSV-L), and a high-dose group of 40 mg/kg resveratrol (RSV-H). After 4 weeks of implant implantation, a silk thread ligation induced peri implantitis model was established in all mice except for the control group. The model group received intervention with physiological saline by gavage, while the drug group received intervention with resveratrol by gavage for 6 consecutive weeks. After 6-week treatment, observe the swelling of the gums around the implant and measure the bone resorption around the mouse implant using micro CT. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in gingival crevicular fluid. HE staining was used to observe the infiltration of inflammatory cells in the surrounding tissues of mouse implants. Protein expression level and phosphorylation level of extracellular regulated protein kinases (ERK), p-ERK, c-Jun N-terminal kinase (JNK), p-JNK, p38 mitogen activated protein kinase (p38 MAPK), p-p38MAPK, nuclear factor kappa-B (NF-κB), p-NF-κB, nuclear factor-κB inhibitory protein (IκΒα), p-IκBα in MAPKs/NF-κB signaling pathway were detected by Western blot (WB). Results Resveratrol group showed reduced tissue edema and decreased alveolar bone resorption. Among them, the high-dose resveratrol group had lighter tissue edema and weaker bone resorption compared to the low-dose group. The micro CT results showed that significant changes in the bone level around the implant were observed in the model group mice at four sites: proximal, distal, buccal, and palatal. High dose resveratrol intervention reduced alveolar bone resorption (PPP>0.05). The ELISA results showed that compared with the model group, the levels of TNF - α and IL-6 in the gingival crevicular fluid of mice in the low-dose and high-dose resveratrol groups were lower (PPPP

Copyright of Journal of Prevention & Treatment For Stomatological Diseases is the property of Journal of Prevention & Treatment For Stomatological Diseases Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Vitexin is a natural flavonoid compound extracted from Vitex leaves or seeds, exhibiting various pharmacological activities including anticancer, antihypertensive, anti-inflammatory, and spasmolytic effects. However, its protective effects on hypertensive nephropathy (HN) and the underlying mechanisms remain unclear. Methods: Spontaneous hypertension rats were fed a high-sugar and high-fat diet for 8 weeks to induce the disease HN model. From the 5th week, the rats were administered vitexin via gavage. Blood pressure was measured biweekly using the tail-cuff method. Histopathological changes were assessed using HE staining, and biochemical analyses were performed to evaluate the effects of vitexin on HN rats. The underlying mechanisms of vitexin treatment were investigated through western blotting. Results: The data demonstrated that vitexin significantly lowered systolic, diastolic, and mean arterial pressures and ameliorated histopathological changes in HN rats. Biochemical analyses revealed that vitexin reduced the levels of creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), total protein (TP), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and advanced glycation end products (AGEs), while increasing the levels of albumin (ALB) and superoxide dismutase (SOD). Western blotting results indicated that vitexin treatment decreased the expression of TNF-α, IL-6, and nuclear factor kappa-B (NF-κB), while increasing the expression of SOD. Conclusion: The findings of this study suggest that vitexin exerts protective effects against HN, providing pharmacological evidence for its potential use in HN treatment. [ABSTRACT FROM AUTHOR]

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Tingting Liu,1,* Haojie Wu,1,* Lin Sun,2 Jianshe Wei1 1Institute for Brain Sciences Research, School of Life Sciences, Henan University, Institute of Neurourology and Urodynamics, Huaihe Hospital of Henan University, Kaifeng, 475004, People’s Republic of China; 2College of Chemistry and Molecular Sciences, Henan University, Kaifeng, 475004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Sun; Jianshe Wei, Email sunlin@vip.henu.edu.cn; jswei@henu.edu.cnBackground: The coronavirus disease 2019 (COVID-19) can lead to neurological symptoms such as headaches, confusion, seizures, hearing loss, and loss of smell. The link between COVID-19 and Parkinson’s disease (PD) is being investigated, but more research is needed for a definitive connection.Methods: Datasets GSE22491 and GSE164805 were selected to screen differentially expressed gene (DEG), and immune infiltration and gene set enrichment analysis (GSEA) of the DEG were performed. WGCNA analyzed the DEG and selected the intersection genes. Potential biological functions and signaling pathways were determined, and diagnostic genes were further screened using gene expression and receiver operating characteristic (ROC) curves. Screening and molecular docking of ibuprofen as a therapeutic target. The effectiveness of ibuprofen was verified by constructing a PD model in vitro, and constructing “COVID19-PD” signaling pathway, and exploring the role of angiotensin-converting enzyme 2 (ACE2) in PD.Results: A total of 13 DEG were screened from the GSE36980 and GSE5281 datasets. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that the DEG were mainly associated with the hypoxia-inducible factor (HIF-1), epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, etc. After analysis, it is found that ibuprofen alleviates PD symptoms by inhibiting the expression of nuclear factor kappa-B (NF-κB), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Based on signal pathway construction, the importance of ACE2 in COVID-19-induced PD has been identified. ACE2 is found to have widespread distribution in the brain. In the 1-methyl-4-phenyl-1,2,3,6-te-trahydropyridine (MPTP)-induced ACE2-null PD mice model, more severe motor and non-motor symptoms, increased NF-κB p65 and α-synuclein (α-syn) expression with significant aggregation, decreased tyrosine hydroxylase (TH), severe neuronal loss, and neurodegenerative disorders.Conclusion: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the risk of PD through an inflammatory environment and downregulation of ACE2, providing evidence for the molecular mechanism and targeted therapy associated with COVID-19 and PD.Keywords: Parkinson’s disease, COVID-19, ibuprofen, nuclear factor kappa-B, angiotensin-converting enzyme 2

Acute pancreatitis (AP) is characterized by elevated intracellular Ca2+ concentrations, mitochondrial dysfunction, and oxidative stress in pancreatic acinar cells. Algal oil (AO) has demonstrated antioxidant and anti-inflammatory properties. This study aims to explore the effects of algal oil on the microenvironment of AP. Rat pancreatic acinar AR42J cells were pretreated with AO containing 0, 50, 100, or 150 μM of docosahexaenoic acid (DHA) 2 h prior to AP induction using sodium taurocholate (STC). After 1 h of STC treatment, AR42J cells exhibited a significant increase in intracellular Ca2+ concentration and the production of amylase, lipase, reactive oxygen species, and pro-inflammatory mediators, including tumor necrosis factor-α and interleukin-6. These STC-induced increases were markedly reduced in cells pretreated with AO. In comparison to cells without AO, those treated with a high dose of AO before STC exposure demonstrated a significant increase in mitochondrial membrane potential and a decrease in lipid peroxidation. Furthermore, STC-activated nuclear factor kappa-B (NF-κB) was attenuated in AO-pretreated cells, as evidenced by a significant decrease in activated NF-κB. In conclusion, AO may prevent damage to pancreatic acinar cells by alleviating intracellular Ca2+ overload, mitigating mitochondrial dysfunction, reducing oxidative stress, and attenuating NF-κB-targeted inflammation.

Purpose: To explore the effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on retinal ischemia-reperfusion injury (RIRI) and the protective effect of N-hydroxy-N'-(4-n-butyl-2-methylphenyl)formamidine (HET0016) on RIRI. Methods: Male Sprague-Dawley rats were randomly divided into the normal control group, experimental model group (RIRI group), experimental solvent group (RIRI + solvent group), and experimental treatment group (RIRI + HET0016 group). Results: The levels of 20-HETE, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in the retina of rats at 24 h after reperfusion were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe the retinal morphological and thickness changes at 24 h, 48 h, and 7 days after reperfusion. The number and localized expression of matrix metalloproteinase-9-positive cells in the retina of the rats at 24 h after reperfusion and the activation and localized expression of retinal microglia at 48 h after reperfusion were measured using an immunohistochemical method. The nuclear metastasis of nuclear factor kappa-B (NF-κB, p65) cells at 24 h after reperfusion was observed using an immunofluorescence method. Conclusion: Overall, 20-HETE might activate microglia to aggravate RIRI by the NF-κB pathway, but HET0016 has significant protective effects for the retina. [ABSTRACT FROM AUTHOR]

Objective: To discuss the effect of rubusoside (RUB) on the spinal cord injury (SCI) and neuroinflammation in the mice, and to clarify its mechanism. Methods: A total of 48 female Kunming mice were randomly divided into sham operation group, SCI group, SCI+low dose of RUB group, and SCI+high dose of RUB group, and there were 12 mice in each group. Spinal cord injury behavior (BBB) scoring method was used to assess the motor function of the hind limbs of the SCI mice; water content method was used to detect the spinal cord edema of the SCI mice; real-time fluorscence quantitative PCR (RT-qPCR) method was used to detect the expression levels of pro-inflammatory cytokines cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) mRNA of the mice in various groups; ELISA method was used to detect the levels of inflammatory factors in serum of the mice in various groups; HE staining was used to observe the pathomorphology of spinal cord tissue of the mice in various groups；immunofluorescence was used to detect the activation of microglia in spinal cord tissue of the mice in various groups; Western blotting method was used to detect the expression levels of related proteins in spinal cord tissue of the mice in various groups. Results: The BBB score analysis results showed that compared with sham operation group, the score of the mice in SCI group was decreased to 0; compared with SCI group, the BBB scores of the mice in SCI+low dose of RUB group and SCI+high dose of RUB group were gradually increased. The spinal cord tissue water content detection results showed that compared with sham operation group, the water content in spinal cord tissue of the mice in SCI group was significantly increased (P<0. 01) ; compared with SCI group, the water contents in spinal cord tissue of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group were significantly decreased (P<0. 01) . The RT-qPCR results showed that compared with sham operation group, the expression levels of COX-2, IL-1β, and TNF-α mRNA in spinal cord tissue of the mice in SCI group were significantly increased (P<0. 001) . Compared with SCI group, the expression levels of COX-2, IL-1, and TNF- α mRNA in spinal cord tissue of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group were significantly decreased (P<0. 001). The ELISA results showed that compared with sham operation group, the levels of IL-1β (P<0. 01) and TNF-α (P<0. 001) in serum of the mice in SCI group were increased; compared with SCI group, the levels of IL-1β and TNF-α in spinal cord tissue of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group were decreased (P<0. 001). The Western blotting results showed that compared with sham operation group, the expression levels of nuclear factor kappa B (NF-κB) inhibitor protein-α (IκB-α), phosphorylated IκB-α (p-IκB-α), phosphorylated p65 (p-p65), p65, phosphorylated p38 (p-p38), phosphorylated extracellular regulated protein kinase (p-ERK), and phosphorylated c-Jun N-terminal kinase (p-JNK) proteins in spinal cord tissue of the mice in SCI group were significantly increased (P<0. 05 or P<0. 001) ; compared with SCI group, the expression levels of IκB- α, p-IκB- α, p-p65, p65, p-p38, p-ERK, and p-JNK proteins in spinal cord tissue of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group were significantly decreased (P<0. 001). The HE staining results showed that compared with sham operation group, the spinal cord tissue of the mice in SCI group had loose organization with the formation of vacuoles, and a large necrotic cavity was present in the center of the spinal cord; compared with SCI group, the central necrotic cavity area of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group was significantly decreased (P<0. 05). The immunofluorescence results showed that compared with sham operation group, the number of positive microglia cells in spinal cord tissue of the mice in SCI group was significantly increased (P<0. 001) ; compared with SCI group, the numbers of positive microglia cells in spinal cord tissue of the mice in SCI+ low dose of RUB group and SCI+ high dose of RUB group were significantly decreased (P<0. 001). Conclusion: Rubusoside can improve the motor function impairment in the SCI mice, mitigate the neuroinflammation in spinal cord tissue, and inhibit the activation of microglia. The mechanism may be related to the downregulation of expression of proteins associated with the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways in spinal cord tissue. [ABSTRACT FROM AUTHOR]

ABSTRACT: Macrophages play a crucial role in both innate and adaptive immunity. However, their abnormal activation can lead to undesirable inflammatory reactions. This study aimed to investigate the effects of glycerol monolaurate (GML), a natural monoester known for its anti-inflammatory and immunoregulatory properties, on avian macrophages using the HD11 cell line. The results indicated that a concentration of 10 μg/mL of GML enhanced the phagocytic activity of HD11 cells (P < 0.05) without affecting cell viability (P > 0.05). GML decreased the expression of M1 macrophage polarization markers, such as CD86 and TNF-α genes (P < 0.05), while increasing the expression of M2 macrophage polarization markers, such as TGF-β1 and IL-10 genes (P < 0.05). GML suppressed ROS production, apoptosis, and the expression of proinflammatory genes (IL-1β and IL-6) induced by LPS (P < 0.05). GML also promoted the expression of TGF-β1 and IL-10 (P < 0.05), both in the presence and absence of LPS exposure. Moreover, GML suppressed the gene expression of TLR4 and NF-κB p65 induced by LPS (P < 0.05), as well as the phosphorylation of NF-κB p65 (P < 0.05). In conclusion, GML exhibited regulatory effects on the polarized state of avian macrophages and demonstrated significant anti-apoptotic and anti-inflammatory properties by suppressing intracellular ROS and the NF-κB signaling pathway.

[INLINE:1] Previous studies have shown that Biochanin A, a flavonoid compound with estrogenic effects, can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury; however, its effect on spinal cord injury is still unclear. In this study, a rat model of spinal cord injury was established using the heavy object impact method, and the rats were then treated with Biochanin A (40 mg/kg) via intraperitoneal injection for 14 consecutive days. The results showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal cord tissue injury, reduced inflammation and oxidative stress in spinal cord neurons, and reduced apoptosis and pyroptosis. In addition, Biochanin A inhibited the expression of inflammasome-related proteins (ASC, NLRP3, and GSDMD) and the Toll-like receptor 4/nuclear factor-κB pathway, activated the Nrf2/heme oxygenase 1 signaling pathway, and increased the expression of the autophagy markers LC3 II, Beclin-1, and P62. Moreover, the therapeutic effects of Biochanin A on early post-spinal cord injury were similar to those of methylprednisolone. These findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling pathways. These findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.

Medium-chain fatty acids and their derivatives are natural ingredients that support immunological functions in animals. The effects of glycerol monolaurate (GML) on intestinal innate immunity and associated molecular mechanisms were investigated using a chicken embryo model. Sixty-four Arbor Acres broiler embryos were randomly allocated into four groups. On embryonic day 17.5, the broiler embryos were administered with 9 mg of GML, which was followed by a 12-h incubation period and a 12-h challenge with 32 μg of lipopolysaccharide (LPS). On embryonic day 18.5, the jejunum and ileum were harvested. Results indicated that GML reversed the LPS-induced decline in villus height and upregulated the expression of mucin 2 (P

Objective: The objective of this study is to evaluate the cytoprotective activity and potential mechanism of hawthorn bioactive polyphenols (HBPs) using human bronchial epithelial (16HBE) cells exposed to benzo(a)pyrene (BaP). Methods: HBPs were isolated by activity-guided separation, and their cytotoxicity was assessed by the methyl thiazolyl tetrazolium (MTT) method. The cytoprotective activity of HBPs against BaP-induced injury in 16HBE cells was determined by the cell counting kit-8 (CCK-8) method. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the effect of HBP-1 on BaP-induced inflammatory factors such as tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-18, IL-10, IL-6 and reactive oxygen species (ROS) in 16HBE cells. Flow cytometry was utilized to explore the effect of HBP-1 on BaP-induced apoptosis in 16HBE cells. Western blotting was conducted to examine the effect of HBP-1 on protein expression related to the aryl hydrocarbon receptor (AhR) and nuclear factor kappa-B (NF-κB) signaling pathways in BaP-induced 16HBE cells. Results: A total of 10 bioactive phenolic compounds were isolated from hawthorn. Among them, HBP-1 exhibited the most significantly cytoprotective activity against BaP-induced inflammatory injury in 16HBE cells. HBP-1 significantly inhibited the oversecretion of IL-1β, IL-18 and TNF-α and the increase in ROS level and BaP-induced apoptosis in 16HBE cells. Western blotting results indicated that HBP-1 could inhibit the activation of the AhR and NF-κB signaling pathways in 16HBE cells induced by BaP. Conclusion: HBP-1 is able to inhibit BaP-induced oxidative stress and excessive production of inflammatory cytokines in 16HBE cells by suppressing the activation of the AhR and NF-κB signaling pathways, highlighting the cytoprotective effect of HBP-1 against BaP-induced damage.

This work aimed to investigate the effects of curcumin (Cur) encapsulated in triblock copolymer nanomicelles on lncRNA GAS5 expression and NF-κB signalling pathway in ischemic stroke rats. Using polycaprolactone (PCL), polyethylene (mPEG), polyglutamic acid (PLG), and Cur as raw materials, Cur-PLG-mPEG-PCL nanoparticles were prepared. Its morphology, particle size, and Zeta potential were analyzed. Then seventy-two SD rats were randomly divided into control (Ctrl) group, model group, model + blank nanomicelles (M + BNM) group, model +80 mg/mL Cur (M + C) group, model +40 mg/mL Cur-nanomicelles (M + CNM (40 mg/mL)) group, and model +80 mg/mL Cur nanomicelle (M + CNM (80 mg/mL)) group. The results showed that mean particle size of Cur-PLG-mPEG-PCL was (148.27 ± 27.44) nm, and mean Zeta potential was (−1.97 ± 0.21) mV. The evaluation time of intelligent optimization algorithm based on Single Shot MultiBox Detector (SSD) was significantly shortened, and average EEG power spectrum of ischemic cerebral pawns was significantly lower than that of the control group at θ, α, β, and γ bands for 4h (p < 0.01). These results indicate that the computer intelligent algorithm can be used to evaluate the behaviour of rats, EEG can reflect the changes of cerebral cortical function, and Cur-PLG-mPEG-PCL can improve neurological function and degree of brain injury. [ABSTRACT FROM AUTHOR]

Objective　To explore the regulatory effect of Mertk expression level on NF-κb pathway in rat Schwann cells and its possible mechanism. Methods　Rat Schwann cells were cultured in vitro，and the expression of Mertk in Schwann cells exposed to high glucose was detected by Western blot. Co-immunoprecipitation was used to detect the interaction between endogenous Mertk and Ikbkb. Western blot was used to detect the expression levels of Ikbkb，P65 and tumor necrosis factor-α in Schwann cells after Mertk silencing. The protein expressions of Mertk， Ikbkb and P65 after silencing Mertk were detected by immunofluorescence. Results　Mertk was expressed in Schwann cells， and the expression level increased with the increase of glucose concentration. Co)immunoprecipitation assay showed that Mertk interacted with Ikbkb in rat Schwann cells. Compared with the control group，the expression level of Mertk was significantly decreased（P < 0.05），while Ikbkb，P65 and TNF-α were significantly increased（ P < 0.05） after knock down expression of Mertk in Schwann cells. Immunofluorescence experiments showed that the fluorescence of Mertk was decreased， and the fluorescence of Ikbkb and P65 was increased in the silenced Schwann cells. Conclusion　After the expression of Mertk is decreased，it can mediate the regulation of NF-κb pathway in Schwann cells through interaction with Ikbkb，and up-regulate the expression of P65 and inflammatory factor TNF-α. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction. One of the important and unresolved issues of pediatric gastroenterology remains study of inflammation mechanisms of the stomach’s mucosa, as well as factors that regulate inflammatory reactions. Nowadays, there are many studies devoted to the research of the nuclear role of factor kappa B (NF-kB) in the regulation of the level of gene expression that control proliferation, cell apoptosis, angiogenesis, and determine the nature and expressiveness of the inflammatory process in adults. However, there are no conclusion regardless the role of NF-kB in the regulation of the mechanisms of inflammation development in the stomach’s mucosa of chronic gastritis (CG) in children. Purpose - to study the level of NF-κB activity depending on the degree of gastric mucosa inflammation of chronic gastritis in children. Materials and methods. We observed 76 children aged 8-16 years with verified chronic gastritis. To verify the diagnosis, all children underwent a morphological examination of the stomach’s mucosa in the fundal and antral departments of the stomach. An indirect streptavidin-peroxidase method of protection using polyclonal antibodies to NF-kB was used for immunohistochemical research. Results. On the basis of the morphological study of gastric biopsies, we discovered inflammatory changes based of lymphocytic infiltration, microcirculatory disorders of the stomach’s mucosa with the subsequent development of stroma lamina propria fibrosis. During the immunohistochemical study of gastric biopsies, a high level of NF-kB expression was noted in the cytoplasm with a pronounced degree of inflammation, atrophy, and lymphocytic infiltration of the stomach’s mucosa. Conclusions. The results of the study indicate the morphological signs of the formation of an early chronic inflammatory process in gastritis in children. The transcription factor NF-kB determines the level of inflammatory activity and plays a leading role in the mechanism of development of chronic gastritis in children. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

Microglia are the brain’s primary innate immune cells, and they are activated and affect pro-inflammatory phenotype or regulatory phenotype after ischemic stroke. Vagus nerve stimulation was shown to activate microglial phenotypic changes and exhibit neuroprotective effects in ischemia/reperfusion injury. In this study, we established rat models of ischemic stroke by occlusion of the middle cerebral artery and performed vagus nerve stimulation 30 minutes after modeling. We found that vagus nerve stimulation caused a shift from a pro-inflammatory phenotype to a regulatory phenotype in microglia in the ischemic penumbra. Vagus nerve stimulation decreased the levels of pro-inflammatory phenotype markers inducible nitric oxide synthase and tumor necrosis factor α and increased the expression of regulatory phenotype markers arginase 1 and transforming growth factor β through activating α7 nicotinic acetylcholine receptor expression. Additionally, α7 nicotinic acetylcholine receptor blockade reduced the inhibition of Toll-like receptor 4/nuclear factor kappa-B pathway-associated proteins, including Toll-like receptor 4, myeloid differentiation factor 88, I kappa B alpha, and phosphorylated-I kappa B alpha, and also weakened the neuroprotective effects of vagus nerve stimulation in ischemic stroke. Vagus nerve stimulation inhibited Toll-like receptor 4/nuclear factor kappa-B expression through activating α7 nicotinic acetylcholine receptor and regulated microglial polarization after ischemic stroke, thereby playing a role in the treatment of ischemic stroke. Findings from this study confirm the mechanism underlying vagus nerve stimulation against ischemic stroke.

Objective: Although the role of obesity and diabetes mellitus (DM) in male infertility is well established, little informationabout the underlying cellular mechanisms in infertility is available. In this sense, nuclear factor kappa-B (NF-kB) hasbeen recognized as an important regulator in obesity and DM; However, its function in the pathogenesis of maleinfertility has never been studied in obese or men who suffer from diabetes. Therefore, the main goal of current researchis assessing NF-kB existence and activity in ejaculated human spermatozoa considering the obesity and diabeticscondition of males. Materials and Methods: In an experimental study, the ELISA technique was applied to analyze NF-kB levels in spermof four experimental groups: non-obese none-diabetic men (body mass index (BMI) 30 kg/m2; OB group; n=30), non-obese diabetic men (BMI 30 kg/m2; OB-DM group; n=30) who were presented to Royan Institute Infertility Center.In addition, protein localization was shown by Immunocytofluorescent assay. Sperm features were also evaluated usingCASA. Results: The diabetic men were older than non-diabetic men regardless of obesity status (P=0.0002). Sperm progressivemotility was affected by obesity (P=0.035) and type A sperm progressive motility was affected by DM (P=0.034). Theconcentration of sperm (P=0.013), motility (P=0.025) and morphology (P

BACKGROUND: Glycogen synthase kinase-3β (GSK3β), fat mass and obesity-associated protein (FTO), and toll-like receptors 4 (TLR4) take on critical significance in different biological processes, whereas their interactions remain unclear. The objective was the investigation of the interaction effect in cerebral ischemia-reperfusion (I/R) injury. METHODS: The function of the cerebral cortex in the mouse middle cerebral artery occlusion (MCAO) model (each group n = 6) and P12 cells oxygen-glucose deprivation/reoxygenation (OGD/R) model was analyzed using short hairpin GSK3β lentivirus and overexpression of FTO lentivirus (in vitro), TLR4 inhibitor (TAK242), and LiCl to regulate GSK3β, FTO, TLR4 expression, and GSK3β activity, respectively. RESULTS: After GSK3β knockdown in the OGD/R model of PC12 cells, the levels of TLR4 and p-p65 were lower than in the control, and the level of FTO was higher than in the control. Knockdown GSK3β reversed the OGD/R-induced nuclear factor kappa-B transfer to the intranuclear nuclei. As indicated by the result, TLR4 expression was down-regulated by overexpressed FTO, and TLR4 expression was up-regulated notably after inhibition of FTO with the use of R-2HG. After the inhibition of the activity of GSK3β in vivo, the reduction of FTO in mice suffering from MCAO was reversed. CONCLUSIONS: Our research shows that GSK3β/FTO/TLR4 pathway contributes to cerebral I/R injury.

Pulmonary hypertension (PH) is a progressive, pulmonary vascular disease with high morbidity and mortality. Unfortunately, the pathogenesis of PH is complex and remains unclear. Existing studies have suggested that inflammatory factors are key factors in PH. Interleukin-6 (IL-6) is a multifunctional cytokine that plays a crucial role in the regulation of the immune system. Current studies reveal that IL-6 is elevated in the serum of patients with PH and it is negatively correlated with lung function in those patients. Since IL-6 is one of the most important mediators in the pathogenesis of inflammation in PH, signaling mechanisms targeting IL-6 may become therapeutic targets for this disease. In this review, we detailed the potential role of IL-6 in accelerating PH process and the specific mechanisms and signaling pathways. We also summarized the current drugs targeting these inflammatory pathways to treat PH. We hope that this study will provide a more theoretical basis for targeted treatment in patients with PH in the future. [ABSTRACT FROM AUTHOR]

Objective: To discuss the therapeutic effect of Saposhnikoviae Radix on rheumatoid arthritis and its effect on the nuclear factor-κB (NF-κB) signaling pathway, and to provide the basis for the treatment of rheumatoid arthritis. Methods: Fifty rats were randomly divided into control group, model group, dexamethasone group, low dose of Saposhnikoviae Radix group, and high dose of Saposhnikoviae Radix group, and there were 10 rats in each group; except for control group, the rats in the other groups were given intradermal injection of type Ⅱ collagen at the root of the tail and left posterior foot to prepare the rheumatoid arthritis models; after the models were prepared successfully, the rats in dexamethasone group were given dexamethasone (2 mg·kg-1 ), the rats in low and high doses of Saposhnikoviae Radix groups were given Saposhnikoviae Radix wild product ( 0. 45 and 0. 90 g·kg-1 ), and equal volume of normal saline was given to the rats in control group and model group. The arthritis index (AI) and foot swelling degrees of the rats in various groups were recorded, the organ coefficients of the rats in various groups were calculated; enzyme-linked immunosorben assay (ELISA) method was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in serum of the rats in various groups, and the expression levels of NF- κB, NF- κB inhibitor α (IkB- α), IκB- α kinase β (IKK- β), cyclooxidase-2 (COX-2), and TNF-α proteins in synovial tissue of the rats in various groups were detected by Western blotting method. Results: Compared with control group, the AI score and swelling degree of foot of the rats in model group were significantly decreased (P<0. 01), while the thymus index was significantly increased (P<0. 01); compared with model group, the AI score and swelling degree of foot of the rats in dexamethasone group and low and high doses of Saposhnikoviae Radix groups were significantly decreased (P<0. 05 or P<0. 01), and the thymus indexes were significantly decreased (P< 0. 01). The ELISA results showed that compared with control group, the levels of TNF-α, IL-1β, and IL-6 in serum of the rats in model group were increased (P<0. 01); compared with model group, the levels of TNF- α, IL-1β, and IL-6 in serum of the rats in dexamethasone group, low and high doses of Saposhnikoviae Radix groups were significantly decreased (P<0. 01). The HE staing results showed that the synovial tissue of the rats in control group was normal, and the synovial tissue of the rats in model group showed hyperplasia accompanied with extensive infiltration of inflammatory cells; compared with model group, the degrees of proliferation of synovial tissue and infiltration of inflammatory cells of the rats in dexamethasone group, low and high doses of Saposhnikoviae Radix groups were decreased. The Western blotting results showed that compared with control group, the expression levels of NF-κB, IKK-β, COX-2, and TNF-α proteins in synovial tissue of the rats in model group were increased (P<0. 01), the expression level of IκB- α protein was decreased (P<0. 01); compared with model group, the expression levels of NF- κB, IKK- β, COX-2, and TNF- α proteins in synovial tissue of the rats in dexamethasone group, low and high doses of Saposhnikoviae Radix groups were decreased (P<0. 01), the expression level of I κB- α protein was increased (P<0. 01). Conclusion: Saposhnikoviae Radix wild product can improve the joint injury by reducing the levels of proinflammatory cytokines and inhibiting the excessive activation of NF-κB signaling pathway in synovial tissue, thus playing a therapeutic role in the rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Neuropathic pain (NP) is a clinically common chronic pain, usually seen in trigeminal neuralgia, postherpetic neuralgia, diabetic NP and other diseases, which seriously affect patients′ sleep and quality of life. Its etiology involves many factors, the pathogenesis is still unclear, the clinical treatment effect is not good. Recently, a large number of studies have shown that nuclear factor kappa-B (NF-κB) plays an important regulatory role in NP by regulating the release of immune-cell-related pro-inflammatory cytokines and pain mediators through transcription, and is involved in the occurrence and maintenance of neuroinflammation. In this paper, by reviewing and summarizing literatures related to NP, the relationship between NF-κB signaling pathway and NP was sorted out, aiming to provide research direction for targeted drug therapy of NP-related diseases. [ABSTRACT FROM AUTHOR]

Objectives T cells adhere to enthesis fibrocartilage via integrins and intrinsically require IL-17RA-mediated signals to maintain their effector function. We analysed CD29+IL-17RA+ T cells in inflamed lesions and peripheral blood in patients with SpA and investigated their association with disease activity and therapeutic response. Methods Transcriptome analysis of synovial fluid T cells from PsA was performed using publicly available bulk cell RNA sequencing data. Blood samples were obtained from healthy controls (n  = 37), RA (n  = 12), IgG4-related disease (IgG4-RD; n  = 12), large vessel vasculitis (LVV; n  = 12) and SpA (n  = 28) and were analysed by flow cytometry. Results T cells in the inflamed joints of PsA showed CD29 and IL-17RA expression. CD29+IL-17RA+ T cells showed enriched CXCR3+CD45RA+ effector cells and activation of spleen tyrosine kinase (Syk), nuclear factor κB (NF-κB) and Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathways. The proportion of peripheral blood CD29+IL-17RA+ T cells was significantly increased in patients with SpA compared with patients with RA, IgG4-RD or LVV and in healthy controls. Based on the ASDAS-CRP scores, the proportion of CD29+IL-17RA+ T cells was positively correlated with disease activity in treatment-naïve patients with active SpA. Anti-IL-17 but not anti-TNF monoclonal antibodies reduced CD29+IL-17RA+ T cells. Conclusions CD29+IL-17RA+ T effector cells with enhanced Syk, NF-κB and JAK-STAT pathways were specifically increased in SpA and were correlated with disease activity, implicating a role of this newly identified T cell population in the pathogenesis. Anti-IL-17 monoclonal antibodies may be effective for patients by reducing this pathogenic T cell population. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease that can cause progressive damage to lung function. At present,the etiology is still unclear, and DNA damage repair may play an important role in the pathogenesis of IPF. When cells are damaged by external stimuli, DNA repair proteins are activated and play the repair function. The process is mainly mediated by poly (ADP-ribose) polymerase-1 and various cytokines, and finally the damaged DNA is repaired. The article reviews the research progress of the relationship between DNA damage repair and IPF. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of norcantharidin (NCTD) on cyclophosphamide (CY)-induced immunosuppression and leukopenia in mice. Methods: Cyclophosphamide (80 mg/kg/day) was intraperitoneally administered to mice from day 1 to 3 and day 9, and from day 4 to 10, NCTD (1, 2 and 4 mg/kg) was intraperitoneally administered. The counts of white blood cells (WBC), red blood cells (RBC) and platelets (PLT) in peripheral blood were determined, followed by the evaluation of mouse spleen and thymus indices. Histopathological examination was performed using hematoxylin-eosin (H & E) staining. In addition, the serum levels of immunoglobulins and cytokines were determined using enzyme-linked immunosorbent assay (ELISA), while plenetic T lymphocyte subsets were assessed by flow cytometry. The expression levels of p65, p-p65, IκBα, and p-IκBα in spleen tissues were determined by immunoblotting. Results: Administration of NCTD (1, 2 and 4 mg/kg) increased blood cell counts, and alleviated injuries on splenocytes and thymocytes in CY-treated mice, accompanied by decline in spleen and thymus indices. -CD4+ and CD8+ T lymphocyte expressions were enhanced, especially at the high dose of NCTD (4 mg/kg). Besides, NCTD at high doses (2 and 4 mg/kg) significantly activated NF-κB pathway. Conclusion: Administration of NCTD alleviates CY-induced leukopenia and immunosuppression in mice through activation of NF-κB pathway, thus providing a lead for the potential treatment of chemotherapy-induced leukopenia and immunosuppression. [ABSTRACT FROM AUTHOR]

Objective: Although the role of obesity and diabetes mellitus (DM) in male infertility is well established, little information about the underlying cellular mechanisms in infertility is available. In this sense, nuclear factor kappa-B (NF-kB) has been recognized as an important regulator in obesity and DM; However, its function in the pathogenesis of male infertility has never been studied in obese or men who suffer from diabetes. Therefore, the main goal of current research is assessing NF-kB existence and activity in ejaculated human spermatozoa considering the obesity and diabetics condition of males. Materials and Methods: In an experimental study, the ELISA technique was applied to analyze NF-kB levels in sperm of four experimental groups: non-obese none-diabetic men (body mass index (BMI) <25 kg/m² ; control group; n=30), obese non-diabetic men (BMI >30 kg/m² ; OB group; n=30), non-obese diabetic men (BMI <25 kg/m² ; DM group; n=30), and obese diabetic men (BMI >30 kg/m² ; OB-DM group; n=30) who were presented to Royan Institute Infertility Center. In addition, protein localization was shown by Immunocytofluorescent assay. Sperm features were also evaluated using CASA. Results: The diabetic men were older than non-diabetic men regardless of obesity status (P=0.0002). Sperm progressive motility was affected by obesity (P=0.035) and type A sperm progressive motility was affected by DM (P=0.034). The concentration of sperm (P=0.013), motility (P=0.025) and morphology (P<0.0001) were altered by obesity × diabetes interaction effects. The NF-kB activity was negatively influenced by the main impact of diabetics (P=0.019). Obesity did not affect (P=0.248) NF-kB activity. Uniquely, NF-kB localized to the midpiece of sperm and post-acrosomal areas. Conclusion: The current study indicated a lower concentration of NF-kB in diabetic men, no effect of obesity on NF-kB was observed yet. Additionally, we revealed the main obesity and diabetes effects, and their interaction effect adversely influenced sperm characteristics. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and mechanistic bases of the intravenous injection of arsenic trioxide at clinical-relevant doses for treating an imiquimod-induced psoriasis-like mouse model. After inducing psoriasis-like skin lesions on the back of mice with imiquimod, mice in each group were injected with a clinical dose of arsenic trioxide through the tail vein. The changes in the gene expression, protein expression and distribution of relevant inflammatory factors were evaluated in the inflicted skin area, for mechanisms underlying the efficacy of intravenous As2O3 intervention. HaCaT cells were used to establish an in vitro psoriasis model and pcDNA3.1-NF-κB overexpression plasmid was transfected into cells to overexpress P65, which further confirmed the role of the NF-κB signaling pathway in the effectiveness of As2O3. Clinical dose of As2O3 can significantly improve abnormal symptoms and pathological changes in psoriasis-like skin lesions induced by IMQ in mice. While IMQ induced abnormal expression and distribution of inflammatory factors in the RIG-I pathway and the microRNA-31 (miR-31) pathway in psoriatic skin tissues, intravenous As2O3 can effectively regulate and restore the normality. The leading role of NF-κB signaling was evidenced in vivo and validated in vitro using the NF-κB-overexpressed HaCaT cell model. Clinical dosage of As2O3 may achieve effective treatment of IMQ-induced psoriatic skin lesions by modulating the NF-κB signaling pathway which regulates both the RIG-I and the miR-31 lines of action. Our data provided strong evidence supporting the claim that systemic As2O3 administration of clinical doses can be a promising treatment for psoriasis patients. [ABSTRACT FROM AUTHOR]

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Background: Inflammatory pain mediated by nuclear factor kappa-B (NF-κB) signal pathway has become an increasingly important clinical issue in the last decade. As a potent antioxidant, Nodakenetin has been shown to have a prominent inhibitory effect on inflammation. However, the therapeutic effects and underlying pharmacological mechanisms of Nodakenetin for inflammatory pain remain unclear. Methods: Intraplanar injection of complete Freund's adjuvant (CFA) was used to establish a model of chronic inflammation pain in C57BL/6 mice. The chronic neuropathic pain model was conducted by the sciatic nerve ligation surgery. QRT-PCR was performed to estimate the RNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Western blot was used to demonstrated the protein levels of phospho-IkappaBα (IκBα), p50, and p65 in HEK293T cells. Results: The bioactive components of the traditional Chinese medicine Notopterygium forbesii boiss mainly include Nodakenetin, isoimperatorin, and pregnenolone. Nodakenetin significantly alleviated CFA-induced inflammatory pain but showed no significant therapeutic effect on surgically induced neuralgia in a mouse model. In contrast, isoimperatorin and pregnenolone did not relieve CFA-induced inflammatory pain. Mechanistically, Nodakenetin inhibited IL-1β-induced activation of the NF-κB pathway and phosphorylation of IκBα in HEK293T cells. Furthermore, Nodakenetin treatment suppressed the expression of IL-6, TNF-α, and IL-1β in mouse bone marrow-derived macrophages. Conclusion: Nodakenetin alleviates inflammatory pain induced by CFA injection in vivo and modulates NF-κB signal pathway in vitro. [ABSTRACT FROM AUTHOR]

Abstract Background The activation of T cells and imbalanced redox metabolism enhances the development of graft-versus-host disease (GVHD). Human placenta-derived mesenchymal stromal cells (hPMSCs) can improve GVHD through regulating T cell responses. However, whether hPMSCs balance the redox metabolism of CD4+IL-10+ T cells and liver tissue and alleviate GVHD remains unclear. This study aimed to investigate the effect of hPMSC-mediated treatment of GVHD associated with CD4+IL-10+ T cell generation via control of redox metabolism and PD-1 expression and whether the Nrf2 and NF-κB signaling pathways were both involved in the process. Methods A GVHD mouse model was induced using 6–8-week-old C57BL/6 and Balb/c mice, which were treated with hPMSCs. In order to observe whether hPMSCs affect the generation of CD4+IL-10+ T cells via control of redox metabolism and PD-1 expression, a CD4+IL-10+ T cell culture system was induced using human naive CD4+ T cells. The percentage of CD4+IL-10+ T cells and their PD-1 expression levels were determined in vivo and in vitro using flow cytometry, and Nrf2, HO-1, NQO1, GCLC, GCLM, and NF-κB levels were determined by western blotting, qRT-PCR, and immunofluorescence, respectively. Hematoxylin-eosin, Masson’s trichrome, and periodic acid-Schiff staining methods were employed to analyze the changes in hepatic tissue. Results A decreased activity of superoxide dismutase (SOD) and a proportion of CD4+IL-10+ T cells with increased PD-1 expression were observed in GVHD patients and the mouse model. Treatment with hPMSCs increased SOD activity and GCL and GSH levels in the GVHD mouse model. The percentage of CD4+IL-10+ T cells with decreased PD-1 expression, as well as Nrf2, HO-1, NQO1, GCLC, and GCLM levels, both in the GVHD mouse model and in the process of CD4+IL-10+ T cell generation, were also increased, but NF-κB phosphorylation and nuclear translocation were inhibited after treatment with hPMSCs, which was accompanied by improvement of hepatic histopathological changes. Conclusions The findings suggested that hPMSC-mediated redox metabolism balance and decreased PD-1 expression in CD4+IL-10+ T cells were achieved by controlling the crosstalk between Nrf2 and NF-κB, which further provided evidence for the application of hPMSC-mediated treatment of GVHD.

As a critical molecule in the onset and sustainment of inflammatory response, the receptor for advanced glycation end products (RAGE) has a variety of ligands, such as advanced glycation end products (AGEs), S100/calcium granule protein, and high-mobility group protein 1 (HMGB1). Recently, an increasing number studies have shown that RAGE ligand binding can initiate the intracellular signal cascade, affect intracellular signal transduction, stimulate the release of cytokines, and play a vital role in the occurrence and development of immune-related diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Alzheimer's disease. In addition, other RAGE signaling pathways can play crucial roles in life activities, such as inflammation, apoptosis, autophagy, and endoplasmic reticulum stress. Therefore, the strategy of targeted intervention in the RAGE signaling pathway may have significant therapeutic potential, attracting increasing attention. In this paper, through the systematic induction and analysis of RAGE-related signaling pathways and their regulatory mechanisms in immune-related diseases, we provide theoretical clues for the follow-up targeted intervention of RAGE-mediated diseases. [ABSTRACT FROM AUTHOR]

Cold atmospheric plasma has been widely applied in medical treatment clinically, especially skin diseases. However, the mechanism of cold atmospheric plasma on the treatment of skin diseases is still undefined. In this study, dinitrofluorobenzene-induced atopic dermatitis mice model was constructed. Cold atmospheric plasma was able to decrease skin cells apoptosis, relieve skin inflammation, ER stress and oxidative stress caused by dinitrofluorobenzene stimulation, which was mediated by cold atmospheric plasma-induced MANF expression. In terms of mechanism, hypoxia-inducible factor-1α expression was increased intracellularly after cold atmospheric plasma treatment, which further bound to the promoter region of manf gene and enhanced MANF transcriptional expression. This study reveals that cold atmospheric plasma has a positive effect on atopic dermatitis treatment, also demonstrates the regulatory mechanism of cold atmospheric plasma on MANF expression via HIF-1α, which indicates the potential medical application of cold atmospheric plasma for atopic dermatitis treatment. [ABSTRACT FROM AUTHOR]

Rosacea is a common cause of ocular surface disease. Specific immunologic features have been implicated in its pathogenesis, including toll-like receptors, mitogen-associated kinase, and nuclear factor kappa-B. Myeolid differentiation factor 88 (MYD88) has been associated with these elements, suggesting a role for this protein in rosacea. This study was designed to compare the expression of MYD88 in the eyelids of patients with and without this disease. Western blotting for MYD88 was performed in 14 control patients and 15 patients with rosacea. Bands were quantified and normalized to actin. Immunohistochemical staining for MYD88 was performed in a different cohort of 12 patients with rosacea and 12 controls, and positively-staining cells were counted across five consecutive 40x fields. Statistical analyses compared the differences between the two groups via a dedicated software package. On western blotting, the mean ratios of MYD88 to actin were 13.8 (standard deviation = 14.1) and 44.3 (standard deviation = 39.6) in control and rosacea patients, respectively (p =.002). On immunohistochemistry, the mean numbers of positively-staining cells were 12.1/40x field (standard deviation = 9.61/40x field) and 27.4/40x (standard deviation = 18.7/40x field) in control and rosacea patients, respectively (p =.0438). MYD88 is enriched in eyelid specimens of rosacea. This finding further implicates the innate immune system in the pathogenesis of rosacea, and is consistent with previous reports regarding the role of this protein in ocular surface disease and the previously-implicated cellular features of the disease. Inhibition of MYD88 may be a successful treatment strategy to manage rosacea. [ABSTRACT FROM AUTHOR]

A. stechmanniana Besser is a semi-shrub plant indigenous to Mongolia, Central Asia, Russia, and Pakistan. Although A. stechmanniana has been used as folk medicine for inflammation, helminth infection, and tumors, the physiological activities of A. stechmanniana have not been fully experimentally validated. We investigated the anti-inflammatory activities and underlying mechanisms of action of A. stechmanniana on LPS-stimulated murine macrophages. Macrophages treated with A. stechmanniana-methanol extract (As-ME) showed the decreased expression of inducible NO synthase and cyclooxygenase-2 and secretion of NO, prostaglandin E2, and pro-inflammatory cytokines. Furthermore, we found As-ME reduced the phosphorylation of c-Jun N-terminal kinase (JNK), which was accompanied by a decrease in c-Jun in the nucleus, and suppressed the phosphorylation of NF-κB inhibitor α and the translocation of NF-κB into the nucleus. The results indicated that As-ME possesses anti-inflammatory effects mediated through inhibition of JNK and NF-κB phosphorylation.

Background: Inflammation is recognized as a hallmark feature of cancer development and progression. The aim of our study was to investigate the significance of serum nuclear factor kappa-B (NF-kB) levels as a circulating marker in the monitoring of inflammation in breast and colon cancer; to show the relationship between NF-kB with inflammatory parameters as tumour necrosis factor-a (TNF-a), soluble TNF-related apoptosis-inducing ligand (sTRAIL), interleukin-6 (IL-6), pentraxin-3 (PTX-3), procalcitonin (PCT), and C-reactive protein (CRP) levels. Methods: Serum NF-kB, TNF-a, sTRAIL, IL-6, PTX-3, PCT, and serum CRP levels were measured using enzyme-linked immunosorbent assay (ELISA) in 40 patients with breast cancer, 40 patients with colon cancer and 30 healthy controls. Results: The serum NF-kB, TNF-a, IL-6, PTX-3, PCT, and serum CRP concentration was significantly higher, and the serum sTRAIL concentration was significantly lower in the patients with breast and colon cancer than in healthy controls. NF-kB was positively correlated with CRP and negatively correlated with sTRAIL. Conclusions: These results suggest that increased NF-kB may decrease the clinical efficacy of sTRAIL in solid tumour cells. There is a relationship between inflammation and carcinogenesis so that the development of cancer occurs with chronic inflammation in breast and colon. The study results have shown that colon and breast cancer patients have increased systemic inflammation, as measured by increased circulating cytokines, and acute-phase proteins, or by abnormalities in circulating cells. NF-kB may combine with other markers of the systemic inflammatory response in prognostic scores in cancer. In addition to surgical resection of the tumour, and conventional radio and chemotherapy for cancer treatment, the use of sTRAIL or other agonists for cancer therapy appeared a new potential therapy.

AIM: To find a new concept to show whether or not apoptosis of retinal ganglion cells (RGCs) can be determined in the histology of acute hyperglycemia in the role of expressed Brn3b gene related to nitric oxide (NO), caspase-3, nuclear factor kappa-B (NF-κB), and tumor necrosis factor-α (TNF-α) as an early predictor of primary open angle glaucoma (POAG) eyes and their associations. METHODS: Experimental in vivo study was carried out using adult male, white Sprague-Dawley rats aged ≥2mo, weighing 150-200 g. The animals were divided into two groups, one group receiving intraperitoneal injection of streptozotociz 50 mg/kg in 0.01 mol/L citric buffer and pH 4.5 and a comparison made with the control group. Retinal tissue was divided into two parts (both experimental and control groups respectively): a) right retina for immunohistochemistry (IHC; caspase-3 and TNF-α); b) left retina was divided into two parts for the purpose of real-time polymerase chain reaction (PCR) test (RNA extraction for Brn3b gene expression analysis) and ELISA test (NO and NF-κB). RESULTS: The experimental group showed a decrease in Brn3b gene expression compared to the control group (1.3-fold lower in 2nd month; 1.1-fold lower in 4th month and 2.5-fold lower in 6th month). However, there was a decrease of NO, caspase-3, and an increase of NF-κB and TNF-α quantity. CONCLUSION: The expression of mRNA Brn3b gene is inversely proportional to apoptosis in RGCs. The quantity of NO, caspase-3, NF-κB and TNF-α is influential in expression of Brn3b in RGCs caused by hyperglycemia in diabetic rats.

Abstract Background Tooth impaction is a common problem in orthodontic practice and in some cases accompanied by pain and pathological changes of surrounding teeth. Understanding the cellular and molecular mechanisms underlying tooth impaction allows finding the most effective orthodontic treatment for patients with impacted teeth (IT). RANK (receptor activator of NF-κB) / RANKL (RANK ligand) / OPG (osteoprotegerin) signaling pathway controls bone resorption and may be involved in the regulation of tooth eruption. The study aimed to evaluate bone remodeling based on the assessment of the RANKL/RANK/OPG status in patients with IT. Methods Bone samples from 18 patients (mean age 25.27 ± 3.34) were divided into 3 groups: 1 – bone tissue of healthy persons (control group); 2 – bone tissue, that was taken near the healthy tooth in patients with tooth impaction; 3 – bone tissue, that was collected near the IT. Levels of RANKL, RANK, OPG, osteocalcin (OC), NF-κB p65 subunit, NFATc1, and caspase-3 were determined by western blotting. The difference between groups was assessed using ANOVA followed by Tukey’s post-hoc test. P-value ≤0.05 was considered statistically significant. Results We established a 1.73-fold elevation of RANK level in the IT area vs. control, indicating the recruitment of preosteoclasts. An increase in RANKL, OPG, and OC content was demonstrated (1.46-, 1.48-, and 1.42-fold respectively), reflecting the high activity of osteoblasts near the IT. Despite the activation of the RANKL/RANK/OPG system in the impaction area, NF-κB and NFATc1 levels did not change compared vs. control, indicating a blocked/delayed process of osteoclastogenesis. We found a decrease in the content of procaspase-3 (1.28-fold), while the level of its active form p17 increased by 2.26 folds near the healthy tooth in patients with IT compared with control. In the area of ​​IT, we observed an increase in procaspase-3 and p17 levels (1.32 and 1.78 folds). This reflects impairments of caspase-3 activation and accumulation of its inactive form in the IT area that may contribute to the tooth eruption failure. Conclusions Tooth impaction may be associated with the disturbances in the caspase-3 cascade activation and the imbalance in the RANKL/RANK/OPG system, and as a result, blocked bone resorption.

Background: Yiqi Huoxue Decoction (YQHXD) is a traditional Chinese medicine that promotes blood circulation, removes blood stasis, facilitates diuresis, and alleviates edema. It is composed of 10 herbal medicines and has extensive application in treating nephrotic syndrome (NS). However, the active components and the potential mechanism of YQHXD for treating NS remain unclear. Methods: We set up a sensitive and rapid method based on Ultra-High Performance Liquid Chromatograph-Mass (UPLC-MS) to identify the compounds in YQHXD and constituents absorbed into the blood. Disease genes were collected through GeneCards, DisGeNET, and OMIM database. Genes of compounds absorbed into blood were predicted by the TCMSP database. We constructed Disease-Drug-Ingredient-Gene (DDIG) network using Cytoscape, established a Protein-protein interaction (PPI) network using String, Gene biological process (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using DAVID. Cellular experiments were performed to validate the results of network pharmacology. Result: A total of 233 compounds in YQHXD and 50 constituents absorbed into the blood of rats were identified. The 36 core targets in the PPI network were clustered in the phosphatidylinositol 3 kinase-RAC serine/threonine-protein kinase (PI3K-AKT) and nuclear factor kappa-B (NF-κB) signaling pathways. Luteolin, Wogonin, Formononetin, and Calycosin were top-ranking components as potentially active compounds. Conclusion: The results of our studies show that YQHXD is able to enhance renal function, alleviate podocyte injury, and improve adriamycin nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Obesity is an excessive increase in body fat mass and triggers chronic inflammation which causes increased fat accumulation in the visceral fat tissue. The aim of this study was to analyze serum zinc (Zn), Zn-alpha 2 glycoprotein (ZAG), peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) levels in morbidly obese patients before and after laparoscopic sleeve gastrectomy (LSG) and determine the association between alteration in body mass index (BMI), the % Excess Weight Loss (% EWL) and the biochemical parameters. Thirty healthy individuals as a control group and 30 morbidly obese patients who had undergone LSG were enrolled in this study. Routine anthropometric and laboratory biochemical parameters in venous blood samples of groups at baseline and 1 and 12 months after LSG were recorded. Significant weight loss was achieved at 1 and 12 months after LSG. At baseline serum ZAG and PPAR-γ levels were lower, while NF-кB levels were higher in morbidly obese patients compared with the control group. Serum ZAG and PPAR-γ levels increased while NF-кB levels decreased 1 month and 12 months after LSG. Decreased %EWL was negatively correlated with changes in NF-кB, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting plasma glucose and insulin at 12 months after LSG in morbidly obese patients. However, %EWL was positively correlated with changes in ZAG. Obesity was associated with down-regulated serum ZAG and PPAR-γ levels while up-regulated serum NF-кB. Our findings suggest that LSG ameliorates upregulating PPAR-γ expression, thereby inhibiting NF-κB-mediated inflammation by weight loss. [ABSTRACT FROM AUTHOR]

B cell lymphoma/leukemia 10 (BCL10) is an important member of the caspase recruitment domain-containing (CARD) protein family, which plays crucial roles in mediating the host inflammatory response. In the present study, a BCL10 homologue was identified from Pacific oyster Crassostrea gigas (designed as Cg BCL10). The full length cDNA of Cg BCL10 was of 897 bp with an open reading frame of 522 bp encoding a polypeptide of 174 amino acids containing a classical CARD domain. The deduced amino acid sequence of Cg BCL10 shared low similarity with the previously identified BCL10s from other species. In the phylogenetic tree, Cg BCL10 was firstly clustered with Cv BCL10 from Crassostrea virginica and then assigned into the branch of invertebrate BCL10s. The mRNA transcripts of Cg BCL10 were highly expressed in gonad, gill, adductor muscle, and haemocytes. After Vibrio splendidus stimulation, the mRNA expression level of Cg BCL10 in haemocytes increased significantly (p < 0.01) at 24, 72 and 96 h. In Cg BCL10-RNAi oysters, the phosphorylation level of mitogen-activated protein kinases (MAPKs), nuclear translocation of NF-κB/Rel and activator protein-1 (AP-1) in haemocytes were inhibited, and the mRNA expressions of inflammatory cytokines including Cg IL17-1, Cg IL17-2, Cg IL17-3, Cg IL17-6 and Cg TNF all decreased significantly (p < 0.01) at 12 h after V. splendidus stimulation. These results suggested that Cg BCL10 regulated the expression of inflammatory cytokines by activating MAPK kinase, and nuclear translocation of NF-κB/Rel and AP-1 to defense pathogen. • A BCL10 homologue (Cg BCL10) was identified from oyster. • The expression of Cg BCL10 in haemocytes was up-regulated after the stimulation of V. splendidus. • Cg BCL10 mediated the phosphorylation of Cg JNK and Cg P38 to activate MAPK inflammatory signaling pathway. • BCL10 regulated Cg NF-κB/Rel and Cg AP-1 to promote the production of inflammatory cytokines. [ABSTRACT FROM AUTHOR]

• Catalpol ameliorated the depressive-like behaviors of CORT-injected mice. • Catalpol weakened serum excessive CORT, ACTH, and CRH levels of depressive-like mice. • Catalpol reversed cerebral excessively inflammatory levels of CORT-injected mice. • Catalpol inhibited cerebral oxidative damage of CORT-induced depressive-like mice. • Catalpol's antidepressive-like mechanism involved dual regulation of NF-κB and Nrf2. This study aimed to investigate the antidepressant effect and mechanism of catalpol on corticosterone (CORT)-induced depressive-like behavior in mice for the first time. As a result, CORT injection induced depressive-like behaviors of mice in behavioral tests, aggravated the serum CORT, adrenocorticotropic hormone, and corticotropin-releasing hormone levels, and conspicuously elevated the phosphorylations of nuclear factor kappa-B (NF-κB) in the hippocampus and frontal cortex, and down-regulated the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2). Furthermore, CORT exposure dramatically augmented the levels of inflammatory factors (interleukin-1β, tumor necrosis factor-α, nitric oxide synthase, and nitric oxide) and lipid peroxidation product malondialdehyde, and attenuated the levels of antioxidants including reduced glutathione, glutathione S-transferase, total superoxide dismutase, and heme oxygenase-1 in the mouse hippocampus and frontal cortex. On the contrary, catalpol administration markedly suppressed the abnormalities of the above indicators. From the overall results, this study displayed that catalpol exerted a beneficial effect on CORT-induced depressive-like behavior in mice possibly via the inhibition of hypothalamus-pituitary-adrenal (HPA) axis hyperactivity, central inflammation and oxidative damage at least partially through dual regulation of NF-κB and Nrf2. [ABSTRACT FROM AUTHOR]

A. stechmanniana Besser is a semi-shrub plant indigenous to Mongolia, Central Asia, Russia, and Pakistan. Although A. stechmanniana has been used as folk medicine for inflammation, helminth infection, and tumors, the physiological activities of A. stechmanniana have not been fully experimentally validated. We investigated the anti-inflammatory activities and underlying mechanisms of action of A. stechmanniana on LPS-stimulated murine macrophages. Macrophages treated with A. stechmanniana-methanol extract (As-ME) showed the decreased expression of inducible NO synthase and cyclooxygenase-2 and secretion of NO, prostaglandin E2, and pro-inflammatory cytokines. Furthermore, we found As-ME reduced the phosphorylation of c-Jun N-terminal kinase (JNK), which was accompanied by a decrease in c-Jun in the nucleus, and suppressed the phosphorylation of NF-κB inhibitor α and the translocation of NF-κB into the nucleus. The results indicated that As-ME possesses anti-inflammatory effects mediated through inhibition of JNK and NF-κB phosphorylation. [ABSTRACT FROM AUTHOR]

Introduction: Low molecular weight heparin (LMWH), a natural sulfated glycosaminoglycan with an affinity for proangiogenic factors, is produced by chemical or enzymatic depolymerization of unfractionated heparin (UFH). Known for its anticoagulant effects, LMWH has recently been reported to have a strong anti-inflammatory effect on colitis, myocarditis, and airway inflammation. However, as a newly-developed drug, its anti-inflammatory mechanism in upper respiratory tract inflammation has not been well-studied.Methods: SD rats were randomly divided into control and experimental groups. The experimental group was established by building an acute nasal sinusitis model with expansion sponges mixed with Streptococcus pneumoniae. Then the experimental group rats were subcutaneously injected with different concentrations of LMWH. After seven consecutive days of injection, some rats were sacrificed, and blood and nasal mucosa samples were taken to determine their inflammation status. The remaining acute sinusitis rats were randomly selected for a week of nasal irrigation with normal saline or saline mixed with different concentrations of LMWH. One week later, rats were sacrificed, and samples of blood and nasal mucosa were taken to determine the inflammation status.Results: Rat nasal mucosa in the model group had obvious inflammation. The degree of nasal mucosa inflammation damage in the experimental group was lower than in the experimental control group, proving that LMWH has a protective effect on the nasal mucosa and that the effect correlates with dosage. Irrigation of the nose with saline mixed with LMWH can improve the anti-inflammatory effect. Protein related to the TLR4-MyD88-NF-κB signaling pathway was activated in the acute sinusitis rat model, and LMWH can significantly inhibit its expression.Conclusion: This is the first report of the anti-inflammatory effect of LMWH in acute upper respiratory tract inflammation, together with an explanation of its anti-inflammatory mechanism. The findings contribute a theoretical basis for its potential anti-tumor effect.

Osteolytic bone disorders are characterized by an overall reduction in bone mineral density which enhances bone ductility and vulnerability to fractures. This disorder is primarily associated with superabundant osteoclast formation and bone resorption activity. Nicorandil (NIC) is a vasodilatory anti-anginal drug with ATP-dependent potassium (KATP) channel openings. However, NIC is adopted to manage adverse cardiovascular and coronary events. Recent research has demonstrated that NIC also possesses anti-inflammatory peculiarity through the regulation of p38 MAPK and NF-κB signaling pathways. Both MAPK and NF-κB signaling pathways play pivotal roles in RANKL-induced osteoclast formation and bone resorption function. Herein, we hypothesized that NIC may exert potential biological effects against osteoclasts, and revealed that NIC dose-dependently suppressed bone marrow macrophage (BMM) precursors to differentiate into TRAP + multinucleated osteoclasts in vitro. Furthermore, osteoclast resorption assays demonstrated anti-resorptive effects exhibited by NIC. NIC had no impact on osteoblast differentiation or mineralization function. Based on Biochemical analyses, NIC relieved RANKL-induced ERK, NF-κB and p38 MAPK signaling without noticeable effects on JNK MAPK activation. However, the attenuation of NF-κB and p38 MAPK activation was sufficient to hamper the downstream induction of c-Fos and NFATc1 expression. Meanwhile, NIC administration markedly protected mice from ovariectomy (OVX)-induced bone loss through in vivo inhibition of osteoclast formation and bone resorption activity. Collectively, this work demonstrated the potential of NIC in the management of osteolytic bone disorders mediated by osteoclasts.

Introduction: Low molecular weight heparin (LMWH), a natural sulfated glycosaminoglycan with an affinity for proangiogenic factors, is produced by chemical or enzymatic depolymerization of unfractionated heparin (UFH). Known for its anticoagulant effects, LMWH has recently been reported to have a strong anti-inflammatory effect on colitis, myocarditis, and airway inflammation. However, as a newly-developed drug, its anti-inflammatory mechanism in upper respiratory tract inflammation has not been well-studied. Methods: SD rats were randomly divided into control and experimental groups. The experimental group was established by building an acute nasal sinusitis model with expansion sponges mixed with Streptococcus pneumoniae. Then the experimental group rats were subcutaneously injected with different concentrations of LMWH. After seven consecutive days of injection, some rats were sacrificed, and blood and nasal mucosa samples were taken to determine their inflammation status. The remaining acute sinusitis rats were randomly selected for a week of nasal irrigation with normal saline or saline mixed with different concentrations of LMWH. One week later, rats were sacrificed, and samples of blood and nasal mucosa were taken to determine the inflammation status. Results: Rat nasal mucosa in the model group had obvious inflammation. The degree of nasal mucosa inflammation damage in the experimental group was lower than in the experimental control group, proving that LMWH has a protective effect on the nasal mucosa and that the effect correlates with dosage. Irrigation of the nose with saline mixed with LMWH can improve the anti-inflammatory effect. Protein related to the TLR4-MyD88-NF-κB signaling pathway was activated in the acute sinusitis rat model, and LMWH can significantly inhibit its expression. Conclusion: This is the first report of the anti-inflammatory effect of LMWH in acute upper respiratory tract inflammation, together with an explanation of its anti-inflammatory mechanism. The findings contribute a theoretical basis for its potential anti-tumor effect. [ABSTRACT FROM AUTHOR]

Osteolytic bone disorders are characterized by an overall reduction in bone mineral density which enhances bone ductility and vulnerability to fractures. This disorder is primarily associated with superabundant osteoclast formation and bone resorption activity. Nicorandil (NIC) is a vasodilatory anti-anginal drug with ATP-dependent potassium (KATP) channel openings. However, NIC is adopted to manage adverse cardiovascular and coronary events. Recent research has demonstrated that NIC also possesses anti-inflammatory peculiarity through the regulation of p38 MAPK and NF-κB signaling pathways. Both MAPK and NF-κB signaling pathways play pivotal roles in RANKL-induced osteoclast formation and bone resorption function. Herein, we hypothesized that NIC may exert potential biological effects against osteoclasts, and revealed that NIC dose-dependently suppressed bone marrow macrophage (BMM) precursors to differentiate into TRAP + multinucleated osteoclasts in vitro. Furthermore, osteoclast resorption assays demonstrated anti-resorptive effects exhibited by NIC. NIC had no impact on osteoblast differentiation or mineralization function. Based on Biochemical analyses, NIC relieved RANKL-induced ERK, NF-κB and p38 MAPK signaling without noticeable effects on JNK MAPK activation. However, the attenuation of NF-κB and p38 MAPK activation was sufficient to hamper the downstream induction of c-Fos and NFATc1 expression. Meanwhile, NIC administration markedly protected mice from ovariectomy (OVX)-induced bone loss through in vivo inhibition of osteoclast formation and bone resorption activity. Collectively, this work demonstrated the potential of NIC in the management of osteolytic bone disorders mediated by osteoclasts. [ABSTRACT FROM AUTHOR]