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Brucellosis is a zoonotic disease caused by Brucella abortus. An efficient immune response is crucial for curing brucellosis. The inflammasome plays a significant role in the immune response. It is unclear which inflammasome is active in acute and chronic brucellosis and how its levels relate to inflammatory cytokines. A total of 40 patients with acute or chronic brucellosis and 20 healthy volunteers had peripheral blood samples collected. The expression levels of AIM2, NLRP3, ASC, and Caspase-1 were determined by a real-time polymerase chain reaction from RNA and serum samples, and IL-1β, IL-18, and IFN-γ were measured by enzyme-linked immunosorbent assay. In the acute brucellosis group, AIM2 expression was significantly higher, while ACS expression was significantly lower than that of healthy volunteers. In patients with chronic brucellosis, AIM2 expression was significantly lower, while Caspase-1 expression was significantly higher than that of healthy volunteers. Serum IL-18 and IFN-γ levels were significantly higher in patients with acute brucellosis than in healthy controls. The IFN-γ level was also significantly higher in patients with chronic brucellosis than in healthy controls. The inflammasome responds differently in different stages of brucellosis. The inflammasome may be the site of action of immune escape in brucellosis., (© 2022. The Author(s).)

Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) is an intracellular sensor that detects endogenous danger signals and environmental irritants to assemble into the NLRP3 inflammasome. Activation of the NLRP3 inflammasome leads to the secretion of the proinflammatory cytokines interleutkin (IL)-1β and IL-18 and induces pyroptosis. Recent studies have shown that the NLRP3 inflammasome participates in the initiation and progression of diabetic atherosclerosis through pathological mechanisms such as β-cell dysfunction, insulin resistance, endothelial cell dysfunction, monocyte adhesion and infiltration, and smooth muscle cell proliferation and migration. In diabetic atherosclerosis, Chinese medicine has been proven effective for the inflammatory response mediated by the NLRP3 inflammasome. This review summarizes the latest progress on the NLRP3 inflammasome in the pathogenesis and potential Chinese medicine treatment of diabetic atherosclerosis., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: To evaluate the relationship between uterine cesarean scar diverticulum (CSD) and subsequent infertility in patients who underwent cesarean section, and determine the effects of pelvic fluid-releasing inflammations on infertility.A retrospective analysis was designed among patients with CSD who were admitted to our hospital from January 1, 2018 to December 31, 2019. A total of 60 patients with CSD and uterine fibroids or benign ovarian tumors who underwent cesarean section were included, and divided into the CSD group and control group. Baseline characteristics of all patients were collected, and the pelvic adhesion scores and the percents of tubal patency were evaluated. Furthermore, the postoperative clinical outcomes were followed up. The levels of inflammatory factors in pelvic fluid were tested using Elisa kits.Preoperative data indicated that the size of the uterine scar diverticulum was (1.68 ± 0.52) cm, the pelvic adhesion scores were higher in CSD group than control group (4.67 ± 0.90 vs 0.47 ± 0.90, P < .05), and 21 of 30 patients with unobstructed fallopian tubes. The levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in patients with CSD were obviously higher than control group (P < .05). After the follow-up, the data displayed that no CSD was found in all patients, the time of menstrual period in patients with CSD was shortened to 7.80 ± 1.27 days, and the myometrial thickness at uterine scar was significantly increased (P < .05). Additionally, the pregnancy rate was increased, and 12 of 30 patients were repregnant. Correlation analysis showed that the levels of inflammatory factors (tumor necrosis factor-α, interleukin-1β, interleukin-6), the size of uterine scar diverticulum, and the myometrial thickness at uterine scar were significantly correlated with subsequent infertility (r = 0.307, 0.083, 0.147, 0.405, 0.291, P < .05).Uterine scar diverticulum repair could improve menstrual prolongation, increased the thickness of myometrium and repregnant rate. Subsequent infertility was positively correlated with uterine scar diverticulum and the levels of inflammatory factors., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: The aim of this study was to explore the potential effect of electroacupuncture (EA) at ST36 on mice bearing breast tumors by regulating inflammatory cytokines to enhance antitumor immunity via vagus nerve., Materials and Methods: Female BALB/c mice were implanted with 4T1-luc2 breast tumor cells to establish a murine mammary cancer model. Tumor growth was evaluated by tumor volume, weight and bioluminescence imaging. Inflammatory conditions in serum and tumor tissue were assessed by cytokines (IL-1β, TNF-α and IL-10) and HE staining. Proportions and functions of CD8 + T cells, NK cells and MDSCs were identified by flow cytometry and western blot. Involvement of vagal efferent components was confirmed by ChAT and c-Fos double labeling immunohistochemistry in dorsal motor nucleus of vagus (DMV). Subdiaphragmatic vagotomy was employed to determine if the effect of EA was mediated by vagus nerve., Key Findings: EA at ST36 reduced the volume and weight of tumors within 22 days after implantation. Proinflammatory cytokines IL-1β and TNF-α in serum, tumor and local inflammatory infiltration were obviously attenuated after EA. Meanwhile, EA intervention significantly augmented the proportion and cytolytic function of CD8 + T cells and NK cells, along with a decline in the accumulation and immunosuppressive activities of MDSCs. Finally, c-Fos expression in ChAT + neurons in DMV increased following EA, and the ameliorating effect of EA was obviously blocked by subdiaphragmatic vagotomy., Significance: EA intervention relieved tumor progression in breast tumor-bearing mice by alleviating inflammation and enhancing antitumor immunity, which was mediated by eliciting efferent vagus nerve activity., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Lupus nephritis (LN) is a kidney disorder that is a critical cause of mortality in patients with systemic lupus erythematosus. The present study aimed to explore the protective role of complement component 1q (C1q) on LN and the underlying mechanism involving the nuclear factor (NF)‑κB singling pathway. MRL/lpr mice served as the LN mouse model, and pcDNA‑C1q was injected into LN mice to determine the role of C1q. C1q mRNA expression was detected using reverse transcription‑quantitative PCR. Urine protein and blood urea nitrogen (BUN) levels were measured, and the histological damage index was determined using H&E staining. ELISA was used to measure the levels of tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑1β, IL‑6, anti‑C1q and anti‑double stranded DNA (dsDNA). CD68‑ and Ki67‑positivity were detected using immunofluorescence, and NF‑κB‑related protein expression was examined using western blotting. C1q mRNA expression was downregulated in renal tissues of LN mice. Overexpression of C1q decreased urine protein, BUN levels and the histological damage index in LN mice. The levels of TNF‑α, IL‑1β, IL‑6, anti‑C1q and anti‑dsDNA in renal tissues of LN mice were also reduced after pcDNA‑C1q treatment. Additionally, overexpression of C1q decreased the CD68‑ and Ki67‑positivity in glomeruli and attenuated the expression of NF‑κB‑related proteins. Phorbol 12‑myristate 13‑acetate, an NF‑κB pathway activator, reversed the inhibitory effect of C1q on inflammation, macrophage infiltration and mesangial cell (MC) proliferation in renal tissues of LN mice. Thus, it was demonstrated that C1q ameliorated inflammation and macrophage infiltration and decreased MC proliferation in renal tissues of LN mice by inhibiting the NF-κB pathway.

China is a larger apiculture producer in the world and more than 120 million kg of bee collected pollens of Chinese wolfberry (WBP) are produced per year. However, the lack of knowledge of the nutritional benefits of WBP limits the use of this natural product in food industry. In the present study, three polysaccharides (WBPPS-1, WBPPS-2 and WBPPS-3) were obtained by ion-exchange chromatography, and their preliminary structures, antioxidant and immunomodulatory activities were investigated. The results showed that WBPPS-1, WBPPS-2 and WBPPS-3 were composed of mannose, rhamnose, galacturonic acid, glucose, galactose, xylose and arabinose with different ratio and their average molecular weights were 1016.3, 878.7 and 901.6 KDa, respectively. In addition, the contents of zinc were far higher than other trace elements in the three polysaccharides, suggesting these polysaccharides probably be polysaccharides‑zinc complex. Moreover, WBPPS-3 exhibited stronger scavenging activities on 2,2'-azinobis-(3-ethyl-benzothiazolin-6-sulfonic acid) and 1,1-diphenyl-2-picrylhydrazyl radicals than WBPPS-1 and WBPPS-2. Likewise, WBPPS-3 exhibited a superior enhanced effect on secretion of nitric oxide, tumor necrosis factor-α, interleukin-1β and interleukin-6 in RAW264.7 cells than other two polysaccharides. Overall, these results suggest that WBPPS-3 has potential to be developed as antioxidant and immunomodulatory ingredients in functional foods, but further animal or clinical studies are required., Competing Interests: Declaration of competing interest The authors have declared that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To investigate the clinical significance of microRNA-146 (miRNA-146) in patients with ulcerative colitis (UC)., Methods: The present prospective observational study included 312 UC patients from August 2015 to August 2018. All patients were divided into mild/moderate and severe groups according to their Sutherland Disease Activity Index (DAI) scores. The clinical activity index and endoscopic index were used to determine the severity of UC. Serum levels of NF-κB, CRP, IL-1β, IL-6, and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). The expression of miRNA-146a was measured using RT-qPCR., Results: The expression of miRNA-146a was significantly lower in both mild/moderate and severe UC patients than the healthy control, and the severe UC patients had the lowest level of miRNA-146a. All inflammatory factors were remarkably higher in severe UC patients. miRNA-146a level was negatively correlated with NF-κB, CRP, IL-1β, IL-6 and TNF-α levels. The ratio of severe UC patients was significantly higher in patients with lower miRNA-146a than in patients with higher miRNA-146a. The levels of NF-κB, CRP, IL-1β, IL-6, and TNF-α were all remarkably higher in patients with lower miRNA-146a. Patients with lower miRNA-146a had higher Sutherland DAI scores, clinical activity index, and endoscopic index., Conclusions: miRNA-146a was down-regulated in UC patients and was negatively correlated with serum levels of inflammatory factors as well as severity of UC patients., (© 2020 by the Association of Clinical Scientists, Inc.)

BACKGROUND Avicularin is a plant-derived flavonoid used in traditional Chinese medicine to treat conditions that include ankle fracture. Bradykinin stimulated MG-63 human osteoblastic osteosarcoma cells has previously been studied in an in vitro model. This study aimed to investigate the effects of avicularin on bradykinin-treated MG-63 human osteoblastic osteosarcoma cells in vitro. MATERIAL AND METHODS MG-63 cells were treated with increasing concentrations of avicularin for 48 hours, followed by 1 μM of bradykinin for 24 h. The MTT assay was used to measure cell viability. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to measure the expression of inflammatory mediators, interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-alpha (TNF-alpha) mRNA and protein, respectively. The expression of oxidative stress factors, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase were measured. Western blot and qRT-PCR were performed to determine p38, p65, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) protein levels and mRNA expression, respectively. RESULTS Avicularin had no cytotoxic effect on MG-63 cells. Avicularin significantly upregulated the expression levels IL-1ß, IL-6, and TNF-alpha in the bradykinin treated group in a dose-dependent manner. Avicularin reduced the level of MDA and the activity of SOD and catalase in the bradykinin treated MG-63 cells, reduced p-p38, p-p65, iNOS, and COX-2 expression, and decreased the p-p38/p38 ratio and the p-p65/p65 ratio in bradykinin treated MG-63 cells in a dose-dependent manner. CONCLUSIONS Avicularin reduced the expression of inflammatory cytokines and the levels of markers of oxidative stress in MG-63 human osteoblastic osteosarcoma cells in vitro.

Osteoarthritis (OA) is a chronic and prevalent degenerative musculoskeletal disorder, which is characterized by articular cartilage degradation and joint inflammation. MicroRNA-203a (miR-203a) has been shown to be involved in multiple pathological processes during OA, but little is known about its function in chondrocyte extracellular matrix (ECM) degradation. In the present study, we aimed to elucidate the effects of miR-203a on articular cartilage degradation and joint inflammation. We observed that the miR-203a level was significantly up-regulated in OA tissues and in an in vitro model of OA, respectively. Inhibition of miR-203a significantly alleviated the interleukin (IL)-1β-induced inflammatory response and ECM degradation in chondrocytes. Moreover, mothers against decapentaplegic homolog 3 (Smad3), a key factor in maintaining chondrocyte homeostasis, was identified as a putative target of miR-203a in chondrocytes. More importantly, inhibition of Smad3 impaired the inhibitory effects of the miR-203a on IL-1β-induced inflammatory response and ECM degradation. Collectively, these results demonstrated that miR-203a may contribute to articular cartilage degradation of OA by targeting Smad3, suggesting a novel therapeutic target for the treatment of OA., (© 2020 The Author(s).)

Cu-Zhi-Yi-Hao (CZYH), an empirical formula of traditional Chinese medicine (TCM), has been used for amnesia treatment in clinical practice. However, its underlying pharmacological mechanism has not been fully illuminated. The current study was designed to investigate the neuroprotective effect of CZYH on a β -amyloid 25-35- (A β 25-35 -) induced learning and memory deficit rat model. CZYH (200, 400, or 800 mg/kg), donepezil (1.0 mg/kg), or distilled water was given to A β 25-35 -stimulated animals for 17 days consecutively. The Morris water maze test revealed that CZYH (400 or 800 mg/kg) administration improved the A β 25-35 -induced cognitive impairments in rats, and Nissl staining demonstrated that CZYH mitigated the A β -caused neuron loss. In addition, CZYH treatment markedly inhibited the activation of microglia as evidenced by a decreased level of IBA-1 and increased YM-1/2 protein expression. The protein expression levels of TNF- α , IL-1 β , and COX-2 were also repressed by CZYH. Besides, CZYH treatment alleviated A β -induced I κ B- α degradation and NF- κ B p65 phosphorylation, as well as reduced the JNK phosphorylation level. In conclusion, the present study suggests that CZYH could improve learning and memory abilities and relieve neuron loss in A β 25-35 -induced rats, at least partly through inhibition of the neuroinflammatory response via inhibiting the JNK-dependent NF- κ B activation, indicating that CZYH might be a promising formula for the treatment of AD., Competing Interests: This study has no financial interests., (Copyright © 2019 Yuanyuan Deng et al.)

BACKGROUND We previously reported that astragaloside IV (As-IV) can alleviate myocardial damage induced by lipopolysaccharide (LPS). However, the anti-inflammatory effects of As-IV following LPS stimulation in mice and H9C2 cardiomyocytes remain unclear. The present study was designed to explore the mechanism of action of As-IV. MATERIAL AND METHODS In vivo, C57BL/6J mice were randomly divided into 5 groups: the control group, the LPS group (10 mg/kg), and 3 LPS groups receiving different doses of As-IV (20, 40, and 80 mg/kg). The protective effect of As-IV on LPS-stimulated H9C2 cardiomyocytes was evaluated in vitro. Cardiac function was detected by echocardiography, and H&E staining was used to evaluate morphologic changes. Cardiomyocyte viability was detected by MTT assay. ELISA was used to detect free fatty acid (FFA), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor alpha (TNF-alpha) levels in mouse serum and in cell supernatant. Adenosine triphosphate (ATP) and adenosine monophosphate (AMP) contents in myocardial tissues and cells were detected by high-performance liquid chromatography. ATP5D and TLR4/NF-kappaB/PPARalpha signaling pathway proteins (TLR4, NF-kappaB, p65, and PPARalpha) were detected by Western blotting. RESULTS As-IV significantly improved cardiac function, myocardial cell viability, and pathological changes and reduced FFA, IL-1ß, IL-6, and TNF-alpha levels. The ATP/AMP ratio in the cardiac tissues of mice and in H9C2 cardiomyocytes was increased compared to that in the LPS group. In addition, As-IV enhanced ATP synthase and PPARalpha protein expression. In H9C2 cardiomyocytes, the p65-specific inhibitor BAY11-7082 exerted similar effects as As-IV. CONCLUSIONS As-IV alleviates LPS-induced myocardial damage by modulating TLR4/NF-kappaB/PPARalpha signaling-mediated energy biosynthesis.

BACKGROUND Salidroside, a natural dietary isothiocyanate, has been widely studied for its multiple effects, including promoting proliferation, anti-inflammation, and anti-apoptosis. In the present study, these effects of Salidroside were explored to assess whether it could prevent osteoarthritis (OA) in vitro. MATERIAL AND METHODS The cytotoxic and proliferating effects of Salidroside on chondrocytes were detected by use of the Cell Counting Kit 8 assay. The expression levels of proteins were detected by Western blot. The cell apoptosis level was assessed by flow cytometry, and the levels of ROS, NO, caspase 3, and caspase 9 were assessed to evaluate the level of apoptosis. The expression level of pro-inflammatory factors was detected by ELISA. RESULTS Our results demonstrated that Salidroside promotes chondrocytes proliferation, inhibits IL-1ß-induced apoptosis and inflammation, and scavenges reactive oxygen species (ROS) and NO of chondrocytes. Salidroside upregulates the level of Bcl-2 and downregulates the level of Bax. Salidroside also inhibits the production of caspase 3/9 and suppresses the phosphorylation of PI3K and AKT. CONCLUSIONS Our results suggest that Salidroside prevents OA by its powerful pro-proliferating, anti-phlogistic, and anti-apoptotic effects by inhibiting PI3K/AKT.

BACKGROUND Chondrocyte apoptosis and catabolism are 2 major factors that contribute to the progression of osteoarthritis (OA). Loganin, an iridoid glycoside present in several herbs, including Flos lonicerae, Cornus mas L, and Strychnos nux vomica, is a valuable medication with anti-inflammatory and anti-apoptotic effects. Our study examines these effects and explores the potential benefits of loganin in the OA treatment. MATERIAL AND METHODS To clarify the roles of loganin in OA and its specific signaling pathway, chondrocytes were administrated with IL-1ß and supplemented with or without LY294002 (a classic PI3K/Akt inhibitor). The apoptotic level, catabolic factors (MMP-3 and MMP-13 and ADAMTS-4 and ADAMTS-5), extracellular matrix (ECM) degradation, and activation of the PI3K/Akt pathway were evaluated using western blotting, PCR, and an immunofluorescent assay. The degenerative condition of the cartilage was evaluated using the Safranin O assay in vivo. The expression of cleaved-caspase-3 (C-caspase-3) was measured using immunochemistry. RESULTS The data suggested that loganin suppressed the apoptotic level, reduced the release of catabolic enzymes, and decreased the ECM degradation of IL-1ß-induced chondrocytes. However, suppressing PI3K/Akt signaling using LY294002 alleviated the therapeutic effects of loganin in chondrocytes. Our in vivo experiment showed that loganin partially attenuated cartilage degradation while inhibiting the apoptotic level. CONCLUSIONS This work revealed that loganin treatment attenuated IL-1ß-treated apoptosis and ECM catabolism in rat chondrocytes via regulation of the PI3K/Akt signaling, revealing that loganin is a potentially useful treatment for OA.

BACKGROUND This study aimed to investigate cognitive function, hippocampal neuronal changes, and the expression of inflammatory cytokines in a mouse model of hepatic ischemia-reperfusion injury. MATERIAL AND METHODS Sixty mice were divided into the sham group, which underwent surgery without vascular occlusion; the I/R1 group, with occlusion of the left hepatic artery and portal vein for 20 min, and reperfusion for 30 min; and the I/R2 group, with occlusion of the left hepatic artery and portal vein for 40 min, and reperfusion for 30 min. At postoperative day 4 and 11, ten mice from each group underwent the Morris water maze (MWM) task. Hippocampal tissues were stained for Nissl bodies. Expression of nuclear factor-κB (NF-κB) and choline acetyltransferase (ChAT) were quantified by immunohistochemistry. Serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Groups I/R1 and I/R2 showed a significantly increased latency in the MWM test between days 5-9, compared with the sham group (P<0.05), with no difference by day 11; the I/R2 group had an initial lower crossing frequency (P<0.05), with no difference by day 18. The I/R2 group showed reduced numbers of Nissl bodies in hippocampal neurons. The I/R1 and I/R2 groups had increased expression of NF-κB, TNF-α, and IL-1β and decreased ChAT. No differences between the groups were found in levels of NF-κB, TNF-α, IL-1β, or ChAT by day 18. CONCLUSIONS A mouse model of hepatic ischemia-reperfusion injury showed transient and reversible cognitive dysfunction, changes in hippocampal neurons, and expression of inflammatory cytokines.

BACKGROUND This study investigated the clinical effect of interventional therapy in ischemic cerebrovascular disease (ICD). MATERIAL AND METHODS A retrospective analysis was performed on 260 ICD patients who were divided into a control group (122 patients, conventional drug treatment) and an observation group (138 patients, interventional therapy plus conventional drug treatment). Enzyme-linked immunosorbent assay was used to examine the expression of IL-1β, IL-6, and NLR. Furthermore, neurological deficit scores and Barthel index scores as well as the correlation of IL-1β, IL-6 and NLR were examined in these 2 groups. RESULTS The expression of IL-1β, IL-6, and NLR significantly decreased in both groups after 1 week or 4 weeks of treatment compared with before treatment (P<0.05). Significant differences in neurological impairment scores were detected between these 2 groups after 4 weeks of treatment (P<0.05), and the control group showed higher neurological deficit scores than did the observation group (P<0.05). Barthel index scores were significantly higher after treatment than before treatment in the control and observation group (P<0.05), and the control group had lower Barthel index scores than did the observation group (P<0.05). Pearson correlation analysis showed that IL-1β, IL-6, and NLR expression were positively correlated in ICD patients (P<0.05). CONCLUSIONS Interventional surgery combined with conventional drug therapy can reduce serum IL-1β and IL-6 levels, decrease neurological impairment, and improve the quality of life of patients. The combined treatment group showed better outcomes than did the group that received the drug alone; therefore, combined therapy is suitable for promoting better clinical outcomes.

BACKGROUND Fractalkine is widely expressed throughout the brain and spinal cord, where it can exert effects on pain enhancement and hyperalgesia by activating microglia through CX3C chemokine receptor 1 (CX3CR1), which triggers the release of several pro-inflammatory cytokines in the spinal cord. Fractalkine has also been shown to increase cytosolic calcium ([Ca2+]i) in microglia. MATERIAL AND METHODS Based on the characteristics of CX3CR1, a G protein-coupled receptor, we explored the role of inositol 1,4,5-trisphosphate (IP3) signaling in fractalkine-induced inflammatory response in BV-2 cells in vitro. The effect and the underlying mechanism induced by fractalkine in the brain were observed using a mouse model with intracerebroventricular (i.c.v.) injection of exogenous fractalkine. RESULTS [Ca2+]i was significantly increased and IL-1β and TNF-α levels were higher in the fractalkine-treated cell groups than in the farctalkine+ 2-APB groups. We found that i.c.v. injection of fractalkine significantly increased p-p38MAPK, IL-1β, and TNF-α expression in the brain, while i.c.v. injection of a fractalkine-neutralizing antibody (anti-CX3CR1), trisphosphate receptor (IP3R) antagonist (2-APB), or p38MAPK inhibitor (SB203580) prior to fractalkine addition yielded an effective and reliable anti-allodynia effect, following the reduction of p-p38MAPK, IL-1β, and TNF-α expression. CONCLUSIONS Our results suggest that fractalkine leads to hyperalgesia, and the underlying mechanism may be associated with IP3/p38MAPK-mediated calcium signaling and its phlogogenic properties.

Background: Sinapis Semen is derived from the dried mature seeds of Sinapis alba L. or Brassica juncea (L.) Czern. et Coss. Traditionally, the seeds from S. alba are called "White Sinapis Semen" while those from B. juncea are called "Yellow Sinapis Semen"., Purpose: The present study aimed to compare the chemical composition and the anti-inflammatory effects of 50% aqueous ethanol extracts of the White Sinapis Semen (EWSS) and Yellow Sinapis Semen (EYSS) using both acute (12-O-tetradecanoylphorbol-acetate (TPA)- and arachidonic acid (AA)-induced mouse ear edema) and chronic (multiple applications of croton oil (CO)) inflammatory models., Methods: The anti-inflammatory effects of EWSS and EYSS were determined by measuring the ear thickness and myeloperoxidase (MPO) activity. The anti-inflammatory mechanism was explored by measuring the protein and mRNA levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in the ear of the TPA-treated mice., Results: The results showed that both EWSS and EYSS significantly decreased the ear thickness in both the TPA- and AA-induced acute models, as well as in the CO-induced chronic model. In addition, EWSS and EYSS could markedly inhibit the MPO activity in the ears of TPA-, AA- or CO-treated mice. Moreover, EWSS and EYSS also remarkably inhibited the protein and mRNA levels of TNF-α and IL-6 in the ears of TPA-treated mice. Comparatively, EWSS exerted more potent anti-inflammatory effect than that of EYSS., Conclusion: Our results revealed that both EWSS and EYSS are effective anti-inflammatory agents against acute and chronic inflammatory processes, and EWSS possess more potent anti-inflammatory effect than EYSS. The anti-inflammatory effect of the two herbs may be mediated, at least in part, by suppressing the mRNA expression of a panel of inflammatory mediators including TNF-α, IL-6 and IL-1β., (Copyright © 2018. Published by Elsevier GmbH.)

BACKGROUND Sinomenine (SIN) is an extract of the Chinese medicinal herb Sinomenium acutum; it has various pharmacological properties, including immunosuppression and anti-inflammation. The present study aimed to investigate whether SIN has an anti-depressant-like effect in a mouse model of depression induced by chronic unpredictable mild stress (CUMS), and to explore the underlying molecular mechanisms. MATERIAL AND METHODS A mouse model of depression was established and treated with different concentrations of SIN (30, 100, or 300 mg/kg). Then, behavioral tests, including sucrose preference test (SPT), forced swimming test (FST), and the tail suspension test (TST), were performed. The levels of norepinephrine (NE), 5-hydroxytryptamine (5-HT), and proinflammatory cytokines (interleukin-1β [IL-1β] interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]) in the hippocampus of mice were detected by ELISA assay. The levels of p-p38, p-p65, NLRP3, ASC, and caspase-1 were measured by Western blot or/and qRT-PCR. RESULTS The results showed that SIN significantly relieved CUMSinduced depressive-like behaviors. Compared with the model mice, SIN treatment significantly increased the sucrose preference of the mice, and the immobility time in the forced swimming and the tail suspension test were shortened. In addition, SIN decreased CUMS-induced reduction in the concentrations of NE and 5-HT in the hippocampus of mice. SIN reduced CUMS-induced increases in the levels of IL-1β, IL-6, and TNF-α in the hippocampus of mice. Furthermore, activation of the p38MAPK-NF-κB pathway and the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome induced by CUMS were inhibited by SIN treatment. CONCLUSIONS In conclusion, our results indicate the antidepressantlike effects of SIN on chronic unpredictable mild stress-induced depression in a mouse model.

Background: Ophiocordyceps sinensis ( C. sinensis ) extracts have been found to have a therapeutic effect on patients with chronic obstructive pulmonary disease (COPD). Silent information regulator 1 (SIRT1) plays an important role in the regulation of inflammatory mediators and correlates with lung function and COPD exacerbations. The objective of this work was to explore the anti-inflammatory effect and preliminary pathways of nucleosides from cultured C. sinensis on RAW264.7 macrophages and COPD mice., Materials and Methods: The nucleosides were extracted from cultured C. sinensis powder and further purified by macroporous resin D101 and glucan G10 columns. Inflammation and oxidative stress models in RAW264.7 macrophages and in mice were established by injection of cigarette smoke extract (CSE). We then examined how the isolated nucleosides regulated the production of the associated inflammatory mediators in vitro and in vivo by enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and Western blot., Results: The nucleosides inhibited inflammatory mediator expression of tumor necrosis factor-α, interleukin-6, interleukin-1β, and nitric oxide in both the CSE-stimulated RAW264.7 macrophages and mice. Moreover, the nucleosides elevated SIRT1 activation and suppressed nuclear factor-κB (NF-κB)/p65 activation in vitro and in vivo. Nucleoside treatment significantly decreased the levels of the inflammatory mediators in the bronchoalveolar lavage fluid (BALF) and serum of the CSE-induced mice. The nucleosides also altered the recruitment of inflammatory cells in BALF and improved characteristic features of the lungs in the CSE-induced mice., Conclusion: These results show that the nucleosides suppressed COPD inflammation through the SIRT1-NF-κB/p65 pathway, suggesting that the nucleosides may be partly responsible for the therapeutic effects of cultured C . sinensis on COPD patients., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

It is well-known that NLRP3 is closely related to the onset of primary gout (PG). However, the relation between NLRP3 gene transcript variants and the occurrence of PG remains unclear. This study was undertaken to evaluate whether NLRP3 gene transcript variants are involved in the occurrence of PG. A total of 44 acute phase PG (APPG), 52 non-acute phase PG (NAPPG) male patients, and 30 male health control (HC) were involved in this study. We measured NLRP3 and its transcript variants 2, 3, 4, 5, and 1 + 6 expressions in the PBMCs, together with the level of IL-1β in the serum. Further, PBMCs of HC were stimulated with MSU crystals. The levels of NLRP3, NLRP3 gene transcript variants 2, 3, 4 mRNA, and protein expressions were significantly lower in the APPG and NAPPG groups than in the HC group (P < 0.05, respectively), and IL-1β expression was significantly higher in the APPG group than in the HC and NAPPG groups (P < 0.05, respectively). Levels of IL-1β and NLRP3-4 mRNA expressions were negatively correlated with APPG group (r = - 0.2828, P = 0.0252). After stimulating PBMCs of HC with MSU crystals, levels of NLRP3, NLRP3-4 mRNA, and NLRP3 protein expressions were reduced significantly (P < 0.05, respectively), and the level of IL-1β in MSU group was increased significantly (P < 0.05). Here, we show that NLRP3-4 transcript variant may be closely related to the occurrence of PG. Thus, NLRP3-4 gene transcript variant may provide a novel target for the diagnosis and therapy of PG.

This study aims to investigate and compare the biomarkers in the gingival crevicular fluid between the Han and Uygur subjects with healthy implants and peri-implantitis.Totally 80 subjects were divided into the H-case (Han patients with peri-implantitis), U-case (Uygur patients with peri-implantitis), H-control (Han subjects with healthy implants), and U-control (Uygur subjects with healthy implants) groups. Cytokine levels in the gingival crevicular fluid were detected, and the dominant bacteria species were analyzed.The matrix metalloproteinase (MMP)-13 level in the gingival crevicular fluid in the U-control group was significantly higher than the H-control group, whereas the C-reactive protein level in the H-control group was significantly higher than in the U-control group. No significant difference was observed in the dominant subgingival bacteria species between the H- and U-control groups. The levels of interleukin (IL)-1β and MMP-8 were significantly higher in the H-case group than the U-case group, whereas the IL-17A level in the U-case group was significantly higher. The shared dominant subgingival bacteria species of the case groups mainly included Prevotella, clostridium, Porphyromonas, treponema, Streptococcus, neisseria, and hemophilus. Moreover, Acinetobacter, Micrococcus, and Moraxella were found to be the specific dominant subgingival bacteria species for the U-case group. In addition, compared with the H-case group, the IL-1β levels were negatively correlated with Acinetobacter, Micrococcus, and Moraxella in the U-case group.Han and Uygur populations with healthy implants and peri-implantitis have differentially expressed cytokines in the gingival crevicular fluid. Moreover, dominant subgingival bacteria species differ between the Han and Uygur populations with peri-implantitis.

Periodontitis is defined as inflammation affecting the supporting tissue of teeth. Periodontal pathogens initiate the disease and induce inflammatory host response. Hypoxia may accelerate the process by producing pro-inflammatory factors. The aim of this study is to investigate the effect of Porphyromonas gingivalis ( P. gingivalis ) lipopolysaccharides (LPS) and Escherichia coli ( E. coli ) LPS in inducing caspase-1 activation in normoxic or hypoxic phases. The results showed that healthy gingiva was in a normoxic phase (HIF-1α negative). However, hypoxia appeared in periodontitis, in which NLRP3, cleaved-caspase-1, interleukin 1 beta (IL-1β) and caspase-1-induced cell death was enhanced in periodontitis specimens. The in vitro experiment showed that P. gingivalis LPS slightly decreased the level of NLRP3 and IL-1β in gingival fibroblasts under normoxia. Surprisingly, hypoxia reversed the effects of P. gingivalis LPS, highly promoted caspase-1 activation and IL-1β maturation. E. coli LPS, a kind of pathogen-associated molecular pattern (PAMP) was chosen to simulate the effect of Gram-negative microbiota. Different from P. gingivalis LPS, E. coli LPS enhanced IL-1β maturation both in normoxia and hypoxia. Moreover, E. coli LPS turned normoxia into hypoxia phase in experimental periodontitis model, which may subsequently propel the inflammatory effect of P. gingivalis LPS. It was concluded that E. coli LPS induced a hypoxic phase, which is a combing pathological factor of P. gingivalis LPS in caspase-1 activating and IL-1β maturation in periodontal inflammation.

Purpose: Interleukin-1β (IL-1β) and IL-18 are products of activated inflammasomes that play central roles in innate immunity and inflammation. This study was aimed to determine the effect of tumor-derived IL-1β and IL-18 on recurrence and survival of patients with localized clear cell renal cell carcinoma (ccRCC) following surgery., Methods: We retrospectively enrolled 267 patients with localized ccRCC undergoing nephrectomy at a single center. Clinicopathologic features, recurrence-free survival (RFS), and overall survival (OS) were recorded. IL-1β and IL-18 levels were assessed by immunohistochemistry in tumor tissues. The Kaplan-Meier method was used to compare survival curves. Cox regression models were used to analyze the effect of prognostic factors on RFS and OS. Concordance index was calculated to assess predictive accuracy., Results: Both high IL-1β and high IL-18 levels were associated with increased risk of recurrence (P<0.001 and P<0.001, respectively) and reduced survival (P<0.001 and P = 0.001, respectively). The combination of IL-1β and IL-18 expression (IL-1β/IL-18 signature) could further refine prognostic stratification. Multivariate analyses confirmed that IL-1β/IL-18 signature was an independent prognostic factor for RFS and OS (P = 0.005 and P = 0.044, respectively). The predictive accuracy of well-established prognostic models improved when the IL-1β/IL-18 signature was added. Notably, the improvement in prediction was mainly observed in patients with low-risk disease., Conclusions: The combined high expression of IL-1β and IL-18 is an independent predictor for poor prognosis in patients with localized ccRCC, and the prognostic value is more pronounced in patients with low-risk disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this study, the acute toxicity of paraquat (PQ) in common carp was determined. Then, the contents and mRNA levels of the cytokines interleukin-1β (IL-1β), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were evaluated following subacute exposure to PQ. The results show that the LC50 of PQ for common carp at 72 and 96 h was 15.962 and 15.106 mg/L, respectively. Moreover, after 7 days of subacute PQ exposure, the IL-1β content in the fish liver and kidney increased, although it decreased in spleen. However, changes in the IFN-γ content showed an irregular trend. The TNF-α content increased in the liver and spleen but decreased in the kidney. Additionally, PQ exposure also induced alterations in the mRNA levels of IL-1β, IFN-γ, and TNF-α. These results suggest that PQ exposure may result in suppression or excessive activation of the immune system in treated fish and lead to immune dysfunction and reduced immunity., (© 2014 Wiley Periodicals, Inc.)

Background: Minimally invasive esophagectomy (MIE) has been advantageous for lowering pulmonary complications compared with open approaches.(1) However, pulmonary complications remain the most common morbidity after surgical resection of esophageal cancer.(2,3) The aim of this prospective, randomized, controlled, clinical trial was designed to see whether low tidal volume (VT) could further minimize pulmonary complications after MIE., Methods: Between June 2011 and July 2012, a total of 101 patients who underwent MIE received left-lung ventilation during thoracoscopic esophagectomy. All patients received left-lung ventilation during thoracoscopic esophagectomy. Patients were randomly assigned to a low VT (5 mL/kg + 5 cm H2O positive end-expiratory pressure) preserved ventilation (PV) group (n = 53) and a conventional VT (8 mL/kg) controlled ventilation (CV) group (n = 48) in the thoracic stage. Alveolar lavage fluid was harvested from the ventilated lung at intubation and at 18 hours after surgery for analysis of interleukin (IL)-1ß, IL-6, and IL-8 levels. Clinical characteristics, including patient demographics, operation features, and changes in oxygenation index, were recorded and analyzed. Pulmonary complications were identified and statistically compared between the 2 groups., Results: The clinical characteristics and operation features were comparable between the 2 groups. IL-1ß, IL-6, and IL-8 expressions in preoperative alveolar lavage fluid were similar between the 2 groups. Significantly lower IL expressions were observed in the PV group than those in the CV group at 18 hours after MIE (IL-1ß, 25.42 ± 31.01 vs 94.96 ± 118.24 pg/mL; IL-6, 30.86 ± 75.78 vs 92.99 ± 72.90 pg/mL; IL-8, 258.75 ± 188.24 vs 403.95 ± 151.44 pg/mL; all P < .05). The 18-hour postoperative oxygenation index was lower in the CV group than that in the PV group (292.85 ± 28.74 vs 326.35 ± 34.43; P = .046). Pulmonary complications were observed in 18 cases of our series, occurring more frequently on the ventilation side (right, 6 cases; and left, 12 cases). All patients were cured by conservative therapy without severe sequelae. The occurrence of pulmonary complications in the PV group was lower than that in the CV group (9.43% vs 27.08%; P = .021)., Conclusions: Lung injury due to intraoperative single-lung ventilation may contribute to pulmonary complications after MIE. Low VT ventilation could decrease ventilation-associated lung inflammation, thus minimizing pulmonary complications after MIE. Further studies, based on a larger volume of populations, are required to confirm these findings., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: Previous studies indicated that cigarette smokers were more likely to develop hypertension, and both smoking and hypertension were associated with inflammation. Whether inflammation mediates the relationship of them is unclear. This study aims to examine whether inflammation mediates the association between smoking and hypertension., Methods: Nine hundred and eighty-four Chinese current smokers from a community-based chronic diseases survey in Guangzhou and Zhuhai were interviewed about sociodemographics, smoking, chronic conditions, and other health-related variables. Hypertension was defined according to 2007 European Society of Hypertension and European Society of Cardiology (ESH-ESC) Practice Guidelines. Inflammatory markers including C-reactive protein (CRP), interleukin (IL)-6, IL-1β, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and vascular cell adhesion molecule-1 (VCAM-1) were measured by flow cytometry. Logistic regressions were performed to assess the mediation of inflammation on the relationship between smoking quantity and hypertension., Results: We observed a positive association between smoking quantity and hypertension (P<0.05). After controlling for potential confounders, daily cigarette consumption was significantly associated with higher level of CRP and VCAM-1 and lower level of TNF-α among six measured inflammatory markers, and the current smokers with hypertension had significantly higher level of MCP-1 and CRP than those smokers who were normotensive. Furthermore, the association between smoking quantity and hypertension was mediated by CRP, which accounted for 58.59% of the estimated causal effect of smoking on hypertension., Conclusion: We have confirmed previous observations that smoking quantity was positively associated with hypertension, and the results of our study suggested that the association between smoking and hypertension was probably mediated by CRP.

Aims: Although anisodamine, a muscarinic acetylcholine receptor antagonist, has been used in China for treating various shocks for many years, the mechanisms are not well understood. Our previous studies have demonstrated anisodamine exerts its cholinergic anti-inflammatory action through indirectly activating α7 nicotinic acetylcholine receptors (α7 nAChR). Because IL-10 is a critical anti-inflammatory factor, we investigated its potential role in the antishock action of anisodamine., Main Methods: C57BL/6 and IL-10 -/- mice were intraperitoneally administered LPS and/or anisodamine, and the 24h survival rate, cytokine production and α7 nAChR expression were examined. In addition, RAW264.7 cells were stimulated with LPS, anisodamine and/or IL-10, and cytokine production and α7 nAChR expression were investigated., Key Findings: Anisodamine dose-dependently increased the 24h survival rate of C57BL/6 mice treated with LPS. The antishock role of anisodamine was significantly attenuated in IL-10 -/- mice. Anisodamine significantly decreased TNF-α and IL-1β production in LPS-treated RAW264.7 cells and C57BL/6 mice. However, it did not increase the level of IL-10 in the same experiments. In RAW264.7 cells, IL-10 treatment increased α7 nAChR expression, which was further augmented in the presence of anisodamine. Spleens from IL-10 -/- mice expressed significantly lower α7 nAChRs levels compared to IL-10 +/+ mice. Although anisodamine markedly increased the expression of α7 nAChRs in spleens from LPS-treated IL-10 +/+ mice, it only induced a marginal increase of the receptor in spleens from LPS-treated IL-10 -/- mice., Significance: These findings demonstrate that IL-10 plays an important role in the antishock action of anisodamine. It acts through upregulating α7 nAChR synergistically with anisodamine., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

A bacterial strain with putative immunomodulatory properties was isolated from Xi'an hot springs in China. Comparison of 16S rRNA gene revealed a 97% similarity between the tested strain (designated XA-1) and Anoxybacillus kamchatkensis. Two compounds isolated from the secondary metabolites of XA-1 were identified by spectral data (infrared, nuclear magnetic resonance and mass spectrometry) as: (1) cyclo (Gly-L-Pro) and (2) cyclo (L-Ala-4-hydroxyl-L-Pro). Two cyclic dipeptides showed stimulatory properties towards a range of parameters when a dose of 20mg kg(-1) body weight was intraperitoneally injected in naive common carp, Cyprinus carpio. Innate immune parameters (serum SOD, lysozyme and bactericidal activity, and phagocytic activity by peripheral blood leucocytes) along with the expression of two immune-related genes (IL-1β and iNOS) in blood were examined after 7, 14, 21, and 28 days of injection. In the absence of infection, immunomodulators should ideally not affect normal physiology and immunity of the host; possible negative outcomes of activated immune responses in the naive state are discussed. Protection by two bacterial dipeptides was assessed in an intraperitoneal injection challenge trial with live Aeromonas hydrophila. Both compounds reduced mortality, with the highest survival rate observed in the group that received compound 2 (80%) followed by the group that received compound 1 (65%) while control group scored the worse (15%). Elucidation of the involved protective mechanisms in carp requires future studies., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Vagus nerve stimulation inhibits proinflammatory cytokine production by signaling through the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). Anisodamine, a muscarinic acetylcholine receptor antagonist, has been used clinically in China for treatment of various shocks, but the mechanism was poorly understood. Here, we tested the hypothesis whether anisodamine attained its antishock effect through activation of alpha7nAChR., Design: : Randomized and controlled in vitro and in vivo study., Settings: Research laboratory and animal facility rooms., Subjects: Sprague-Dawley rats, Kunming mice, alpha7nAChR-deficient mice, and RAW264.7 cells., Interventions: Sprague-Dawley rats were injected with lipopolysaccharide (LPS) (15 mg/kg, intravenous) to induce septic shock. Methyllycaconitine, a selective alpha7nAChR antagonist, was administered (10 mg/kg, intraperitoneal) 10 minutes before anisodamine (10 mg/kg, intravenous). Mean arterial pressure was monitored and cytokines were analyzed 2 hours after the onset of LPS. In vagotomized mice and alpha7nAChR-deficient mice, the antishock effect of anisodamine was appraised, respectively. RAW264.7 cells were stained by fluorescein isothiocyanate- labeled-alpha-bungarotoxin and the fluorescence intensity was observed. Mice peritoneal macrophages were pretreated and stimulated with LPS, and tumor necrosis factor (TNF)-alpha in the supernatant was measured by enzyme-linked immunosorbent assay., Measurements and Main Results: Methyllycaconitine significantly antagonized the beneficial effect of anisodamine on mean arterial pressure and TNF-alpha, interleukin-1beta expression in response to LPS. The antishock effects of anisodamine were markedly attenuated in vagotomized mice and alpha7nAChR-deficient mice. In vitro, anisodamine significantly augmented the effect of acetylcholine on fluorescence intensity stained with fluorescein isothiocyanate-labeled-alpha-bungarotoxin and TNF-alpha production stimulated with LPS., Conclusion: These findings demonstrate that the antishock effect of anisodamine is intimately linked to alpha7nAChR-dependent anti-inflammatory pathway.