scholarly journals Blockade of glutamate receptor ameliorates lipopolysaccharide-induced sepsis through regulation of neuropeptides

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Zhai Zhe ◽  
Bi Hongyuan ◽  
Qiao Wenjuan ◽  
Wang Peng ◽  
Liu Xiaowei ◽  
...  

Glutamate receptors (N-methyl-d-aspartate receptor (NMDAR)) are expressed mainly in the central nervous system (CNS), but several potentially important exceptions are worth mentioning. Recently, NMDAR, a glutamate receptor, has been reported to be found in the lungs. NMDAR is activated in acute lung injury (ALI). Here, the present experiment was designed to examine whether NMDAR blockade (MK-801) ameliorates ALI through affecting neuropeptides in LPS-induced sepsis animal models. Male Kunming mice were divided into control group, LPS group, control + MK-801 group, and LPS + MK-801 group. Bronchoalveolar lavage fluid (BALF) was collected and evaluated. The lung histological pathology was assayed by immunocytochemistry staining. Western blot was used to measure PGP9.5, substance P (SP), and vasoactive intestinal polypeptide (VIP). Results showed that LPS-induced mice animal models were ameliorated by co-treatment with the MK-801, an uncompetitive NMDAR antagonist. Moreover, the protective effects of MK-801 attributed to the increased secretion of VIP and decreased secretion of SP. The results of the present study indicated that the blockade of NMDAR may represent a promising therapeutic strategy for the treatment of sepsis-associated ALI through regulation of neuropeptides.

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Zhigang Wang ◽  
Xueting Cai ◽  
Zhonghua Pang ◽  
Dawei Wang ◽  
Juan Ye ◽  
...  

Background. Yupingfeng Pulvis (HFBP) had played an active role in many diseases, especially respiratory tract infections. Exploring the possible prevention mechanism of HFBP may provide new ideas in clinical applications for this well-known herbal formula.Purpose. To study the possible mechanisms of therapy effect of HFBP on asthma mice via regulating the balance of Tregs and Th17 cells.Method. The female BALB/c mice were divided into five groups: control group, model group, prednisone (5.5 mg/kg) group, and 22 g/kg HFBP and 44 g/kg HFBP groups. Ovalbumin was used to make the asthma model of mice; the drug was ig administered daily after atomization for consecutive 15 d. The mice were killed after the last administration. The paraffin-embedded tissue sections of the lungs were stained by H&E. Tregs and Th17 cells in bronchoalveolar lavage fluid were detected by flow cytometry. IL-4, TGF-β, and TNF-αin the serum were detected by ELISA assay.Results. HFBP could alleviate the inflammation in the lung tissue of mice, decrease the proportion of Th17 cells, and increase the proportion of Treg cells in bronchoalveolar lavage fluid. HFBP could decrease IL-4 and TNF-αlevel and increase TGF-βlevel in blood.Conclusion. HFBP could treat the asthma through impacting the balance of Th17 cells and Treg cells as well as the levels of related inflammatory cytokines in asthma mice.


Author(s):  
Narges Marefati ◽  
Amin Mokhtari-Zaer ◽  
Farimah Beheshti ◽  
Sareh Karimi ◽  
Zahra Mahdian ◽  
...  

Abstract Background Modulatory effects of soy extract and estradiol on the central nervous system (CNS) have been reported. The effect of soy on scopolamine-induced spatial learning and memory in comparison to the effect of estradiol was investigated. Materials and methods Ovariectomized rats were divided into the following groups: (1) control, (2) scopolamine (Sco), (3) scopolamine-soy 20 (Sco-S 20), (4) scopolamine-soy 60 (Sco-S 60), (5) scopolamine-estradiol 20 (Sco-E 20) and (6) scopolamine-estradiol 60 (Sco-E 60). Soy extract, estradiol and vehicle were administered daily for 6 weeks before training in the Morris water maze (MWM) test. Scopolamine (2 mg/kg) was injected 30 min before training in the MWM test. Results In the MWM, the escape latency and traveled path to find the platform in the Sco group was prolonged compared to the control group (p < 0.001). Treatment by higher doses of soy improved performances of the rats in the MWM (p < 0.05 – p < 0.001). However, treatment with both doses of estradiol (20 and 60 μg/kg) resulted in a statistically significant improvement in the MWM (p < 0.01 – p < 0.001). Cortical, hippocampal and serum levels of malondialdehyde (MDA), as an index of lipid peroxidation, were increased which was prevented by soy extract and estradiol (p < 0.001). Cortical, hippocampal as well as serum levels of the total thiol, superoxide dismutase (SOD) and catalase (CAT) in Sco group were lower than the control group (p < 0.001) while they were enhanced when the animals were treated by soy extract and estradiol (p < 0.01 – p < 0.001). Conclusions It was observed that both soy extract and estradiol prevented learning and memory impairments induced by scopolamine in ovariectomized rats. These effects can be attributed to their protective effects on oxidative damage of the brain tissue.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Qidong Zhuang ◽  
Hongying Ma ◽  
Yun Zhang ◽  
Lei Chen ◽  
Li Wang ◽  
...  

Background. We evaluated the utility of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) for the diagnosis of invasive pulmonary aspergillosis (IPA) in nonneutropenic patients. Methods. A total of 183 patients were included in the final analysis. Bronchoscopies and the detection of GM in BALF were all performed on them. Results. Ten cases of IPA were diagnosed. ROC data demonstrated that, for diagnosing IPA, an optimal cutoff value for GM in BALF of 0.76 yielded a sensitivity of 100.0% and a specificity of 76.2%. Symptoms and radiological findings had no significant difference between proven or probable IPA group and non-IPA group. In our case-control analysis, although nine patients with false-positive results received treatment with Piperacillin/tazobactam, there was no significant difference between case and control group. Conclusions. BALF GM detection is a valuable adjunctive diagnostic tool. Our retrospective study suggests that the optimal value of GM detection in BALF is 0.76 in nonneutropenic patients.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mingyue Yang ◽  
Fanzheng Meng ◽  
Man Gao ◽  
Genhong Cheng ◽  
Xiaosong Wang

AbstractHost immune response may be involved in the pathogenesis of children Mycoplasma pneumoniae pneumonia (MPP). In the current study, we investigated the alterations of cytokines levels among control, mild MPP and severe MPP children to determine whether cytokine signatures associate with MPP and correlate with disease severity. We measured 13 cytokines in bronchoalveolar lavage fluid (BALF) of 88 children with MPP and 26 children with foreign body aspiration (FB) using a Luminex system. Linear discriminant analyses were performed to develop predictive models of mild MPP and severe MPP on these children. We observed nearly complete separations of severe MPP group, mild MPP group and control group in linear discriminant analyses. Eleven cytokines significantly increased in children with MPP, and seven cytokines had statistically significant upward linear trends correlated with MPP severity. In addition, compared to control group, both IFNγ/IL4 ratio and IFNγ/IL13 ratio increased in mild MPP and severe MPP groups. Our results suggest that children MPP can alter BALF cytokines signatures which associate with disease severity and can be characterized by a distinct airway molecular phenotype that has elevated Th1/Th2 ratios.


2017 ◽  
Vol 32 (1) ◽  
pp. 132-140 ◽  
Author(s):  
Rong Biaoxue ◽  
Cai Xiguang ◽  
Liu Hua ◽  
Fu Tian ◽  
Gao Wenlong

Background Annexin A1 has been implicated in various tumor types, but few studies have investigated its involvement in lung cancer. The purpose of this investigation was to quantify the annexin A1 level in bronchoalveolar lavage fluid (BALF) and analyze its usefulness in lung cancer diagnosis. Methods Annexin A1 expression was measured by immunohistochemistry and enzyme immunoassay. The sensitivity and specificity of annexin A1 for distinguishing lung cancer were determined by receiver operator characteristic (ROC) curves. Results Tumor tissues, BALF and serum of patients with lung cancer contained higher levels of annexin A1 than those of the control group of patients with benign lung diseases. Moreover, an increased level of BALF annexin A1 was closely correlated with lymphatic invasion and malignant progression of lung cancer. The sensitivity and specificity of BALF annexin A1 for distinguishing lung cancer were 94.2% and 90.2%, respectively. Conclusions Increased annexin A1 in BALF was correlated with lymphatic invasion and malignant progression of lung cancer, suggesting that it could be an indicator for discerning lung cancer and predicting outcome.


2013 ◽  
Vol 57 (8) ◽  
pp. 3883-3888 ◽  
Author(s):  
Koichi Yamada ◽  
Katsunori Yanagihara ◽  
Norihito Kaku ◽  
Yosuke Harada ◽  
Yohei Migiyama ◽  
...  

ABSTRACTAcinetobacter baumanniiis one of the main pathogens that cause ventilator-associated pneumonia (VAP) and is associated with a high rate of mortality. Little is known about the efficacy of macrolides againstA. baumannii. In order to confirm the efficacy of azithromycin (AZM) against VAP caused by multidrug-resistantA. baumannii(MDRAB), we used a mouse model that mimics VAP by placement of a plastic tube in the bronchus. AZM (10 and 100 mg/kg of body weight) was administered subcutaneously every 24 h beginning at 3 h after inoculation. Phosphate-buffered saline was administered as the control. Survival was evaluated over 7 days. At 48 h postinfection, mice were sacrificed and the numbers of viable bacteria in lungs and bronchoalveolar lavage fluid were compared. Histopathological analysis of lung specimens was also performed. The treatment groups displayed significantly longer survival than the control group (P< 0.05). AZM did not have an antimicrobial effect. Histopathological examination of lung specimens indicated that the progression of lung inflammation was prevented in the AZM-treated groups. Furthermore, total cell and neutrophil counts, as well as cytokine levels, in bronchoalveolar lavage fluid were significantly decreased (P< 0.05) in the AZM-treated groups. AZM may have a role for the treatment of VAP with MDRAB because of its anti-inflammatory effects.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Fatma Kermeoğlu ◽  
Umut Aksoy ◽  
Abdullah Sebai ◽  
Gökçe Savtekin ◽  
Hanife Özkayalar ◽  
...  

Aim. The aim of this study was to investigate the possible therapeutic impacts of two pineal hormones, melatonin and 5-methoxytryptophol (5-MTX), in a rat model of acute pulpitis by analyzing biochemical and histopathological parameters. Methods. This research was done using 32 male and female Wistar albino rats with weight between 200 and 250 g. The rats were randomly divided into four groups: a control group (rats without any treatment), acute pulpitis (AP) group, AP+melatonin group, and AP+5-MTX group. In the AP-induced groups, the crowns of the upper left incisors were removed horizontally. Lipopolysaccharide solution was applied to the exposed pulp tissue before the canal orifices were sealed with a temporary filling material. Melatonin (10 mg/kg) and 5-MTX (5 mg/kg) were administered intraperitoneally. The rats were sacrificed 24 hours after pulp injury, and trunk blood and pulp samples were collected. The concentrations of TNF-α, IL-1β, MMP-1, and MMP-2 in sera and pulp samples were determined using ELISA assay kits. Results. TNF-α, IL-1β, MMP-1, and MMP-2 levels in the serum and pulp tissues were considerably higher in the AP group than the control group ( p < 0.01 ‐ 0.001 ). In the AP+melatonin and AP+5-MTX groups, TNF-α, IL-1β, MMP-1, and MMP-2 levels in the serum and pulp tissues were significantly lower than in the AP group ( p < 0.05 ‐ 0.001 ). Conclusions. Both melatonin and 5-MTX provided protective effects on acute pulpitis, which indicates they may be promising as a therapeutic strategy for oral disease.


1987 ◽  
Vol 62 (4) ◽  
pp. 1398-1404 ◽  
Author(s):  
F. J. Derksen ◽  
J. S. Scott ◽  
R. F. Slocombe ◽  
N. E. Robinson

We assessed the effect of aerosol Micropolyspora faeni challenge in two groups of ponies by measuring lung function, airway reactivity to aerosol histamine, and bronchoalveolar lavage fluid cytology. One group of ponies was sensitized by subcutaneous injection of M. faeni in complete Freund's adjuvant, and the other group served as control. In both groups of ponies, measurements were made at base line and 5 h after aerosol administration of 30 ml of saline or 30 ml of 1% wt/vol particulate M. faeni antigen in saline. Saline challenge had no effect on any of the measured variables. M. faeni challenge had no effect on pulmonary mechanics or gas exchange in the control group but significantly increased respiratory frequency and minute ventilation and decreased arterial CO2 tension in the sensitized ponies. In both groups of ponies, aerosol M. faeni challenge significantly increased total white blood cell count and neutrophil numbers in bronchoalveolar lavage fluid while large mononuclear cell numbers decreased. Airway responsiveness was unaltered by saline or M. faeni challenge in both pony groups. We conclude that aerosol M. faeni challenge induces pulmonary neutrophilia and abnormalities of ventilation but is not accompanied by airway hyperresponsiveness in sensitized ponies.


2013 ◽  
Vol 32 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Bahram Nikkhoo ◽  
Naseh Sigari ◽  
Bayazid Ghaderi ◽  
Abdolrahim Afkhamzadeh ◽  
Namam-Ali Azadi ◽  
...  

Summary Background: This study aimed to determine adenosine deaminase (ADA) activity as a possible screening tool in lung cancer patients. Methods: Blood samples were collected from 30 subjects with positive pathological tests and 62 patients with negative pathological tests as a control group. The enzymatic activity of total ADA and its isoenzymes was determined. Results: tADA and ADA2 isoenzyme activity was significantly higher in cancerous patients compared to benign controls in serum and BAL fluid. Using a cut-off level of respectively 35.22 U/L and 31.80 U/L for BAL total ADA and ADA2, sensitivity and specificity were 100% and 81% for total ADA and 95% and 98% for ADA2. Conclusions: Adenosine deaminase may play important roles in the pathophysiology of lung cancer and because of its might be considered as a useful screening tool among the other markers in lung cancer diagnosis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mengting Li ◽  
Jia Ke ◽  
Yiqing Deng ◽  
Chunxiang Chen ◽  
Yichen Huang ◽  
...  

Background: Stroke is the second leading cause of death in human life health, but current treatment strategies are limited to thrombolytic therapy, and because of the tight time window, many contraindications, and only a very small number of people can benefit from it, new therapeutic strategies are needed to solve this problem. As a physical barrier between the central nervous system and blood, the blood-brain barrier (BBB) maintains the homeostasis of the central nervous system. Maintaining the integrity of the BBB may emerge as a new therapeutic strategy. Liquiritin (LQ) is a flavonoid isolated from the medicinal plant Glycyrrhiza uralensis Fisch. ex DC. (Fabaceae), and this study aims to investigate the protective effects of LQ on brain microvascular endothelial cells (BMECs), to provide a new therapeutic strategy for stroke treatment, and also to provide research ideas for the development of traditional Chinese medicine (TCM).Methods: The protective effects of LQ on HBMECs under the treatment of hypoxia reoxygenation (H/R) were investigated from different aspects by establishing a model of H/R injury to mimic ischemia-reperfusion in vivo while administrating different concentrations of LQ, which includes: cell proliferation, migration, angiogenesis, mitochondrial membrane potential as well as apoptosis. Meanwhile, the mechanism of LQ to protect the integrity of BBB by antioxidation and inhibiting endoplasmic reticulum (ER) stress was also investigated. Finally, to search for possible targets of LQ, a proteomic analysis approach was employed.Results: LQ can promote cell proliferation, migration as well as angiogenesis and reduce mitochondrial membrane potential damage and apoptosis. Meanwhile, LQ can also reduce the expression of related adhesion molecules, and decrease the production of reactive oxygen species. In terms of mechanism study, we demonstrated that LQ could activate Keap1/Nrf2 antioxidant pathway, inhibit ER stress, and maintain the integrity of BBB. Through differential protein analysis, 5 disease associated proteins were found.Conclusions: Studies have shown that LQ can promote cell proliferation, migration as well as angiogenesis, and reduce cell apoptosis, which may be related to its inhibition of oxidative and ER stress, and then maintain the integrity of BBB. Given that five differential proteins were found by protein analysis, future studies will revolve around the five differential proteins.


Sign in / Sign up

Export Citation Format

Share Document